Enhancing tissue penetration of physiologically active
steroidal agents with DMSC
Inventor: HERSCHLER ROBERT J
COMPOSITIONS FOR TOPICAL APPLICATION FOR ENHANCING TISSUE
PENETRATION OF PHYSIOLOGICALLY ACTIVE AGENTS WITH DMSO
Inventor: HERSCHLER R
ENHANCING TISSUE PENETRATION OF PHYSIOLOGICALLY ACTIVE
STEROIDAL AGENTS WITH DMSO
Inventor: HERSCHLER R
ENHANCING TISSUE PENETRATION OF PHYSIOLOGICALLY ACTIVE AGENTS
Inventor: HERSCHLER ROBERT JOHN
EC: A61K9/00M3; A61K47/20 IPC:
A61K45/08; A61K47/20; A61K45/00 (+2)
*********** Publication info:
USE OF TARGETED OXIDATIVE THERAPEUTIC FORMULATION IN TREATMENT
OF VIRAL DISEASES
Inventor: HOFMANN ROBERT
Use of targeted oxidative therapeutic formulation in bone
Use of targeted oxidative therapeutic formulation in treatment
of diabetes and obesity
Use of targeted oxidative therapeutic formulation in treatment
Therapeutic DMSO solvates of
Use of targeted oxidative therapeutic formulation in
USE OF TARGETED OXIDATIVE THERAPEUTIC FORMULATION IN ENDODONTIC
Use of targeted oxidative therapeutic formulation in treatment
Use of targeted oxidative therapeutic formulation in treatment
USE OF TARGETED OXIDATIVE THERAPEUTIC FORMULATION IN TREATMENT
USE OF TARGETED OXIDATIVE THERAPEUTIC FORMULATION IN TREATMENT
OF AGE-RELATED MACULAR DEGENERATION
Use of targeted oxidative therapeutic formulation in treatment
of diabetes and obesity
Use of targeted oxidative therapeutic formulation in treatment
of age-related macular degeneration
Use of targeted oxidative therapeutic formulation in treatment
of viral diseases
THERAPEUTIC ANTI-FUNGAL NAIL PREPARATION
TREATMENT OF CARBON MONOXIDE POISONING
Dimethylformamide and other polar compounds for the treatment
of wasting syndrome and HIV infections
THERAPEUTIC DIMETHYL SULFOXIDE COMPOSITION AND METHODS OF USE
PHARMACEUTICAL COMPOSITIONS AND THEIR USE IN THE PROPHYLAXIS
AND/OR TREATMENT OF CERTAIN DISEASES
Therapeutic compositions comprising dimethylsulphoxide
No later than 1968, it was discovered that there was another
product that could target cancer cells, but this product
actually bound to the chemotherapy. In this article (which will
be linked to below):
* "Haematoxylon [a dye] Dissolved in
Dimethylsulfoxide [DMSO] Used in Recurrent Neoplasms [i.e.
cancer cells or tumor cells]," by E. J. Tucker, M.D., F.A.C.S.,
and A. Carrizo, M.D. in International Surgery, June 1968, Vol
49, No. 6, page 516-527
it was shown that DMSO targeted cancer cells!! Is it any wonder
that the referee of the article stated:
* "In spite of my criticisms, there are some
parts of this study which do interest me very much. The fact
that the Haematoxylon [a color die, which allowed the
researchers to see which cells absorbed the DMSO and
haematoxylon] and D.M.S.O. solution had a particular affinity
for neoplasms [i.e. cancerous cells], and did not stain other
tissues in animals could be most significant."
In other words, these researchers had discovered something that
could bind to chemotherapy and then target cancer cells. They
had found a second "magic bullet"!!
The combination of DMSO and Haematoxylon was being used as a
cure for cancer in this study. The combination performed very,
very well. However, it was unfortunate that chemotherapy was
used in many of the cases. Since DMSO binds to some types of
chemotherapy (which was probably not known at the time), it is
not know whether the success of the treatment was caused by the
DMSO/chemotherapy combination or the DMSO/haematoxylon
In any case, even though both DMSO and haematoxylon are purely
non-toxic and purely natural (both come from trees), this is not
a treatment that should be used at home. It can cause severe
internal bleeding in some cases. It is far beyond the scope of
this article to get into the use of this treatment.
The point is that the "magic bullet" had been found, which this
website calls "DMSO Potentiation Therapy (DPT)." Obviously,
further research using DMSO and chemotherapy, or DMSO and
haematoxylon, never happened.
Why don't you ask your oncologist why research on the magic
bullet discovered in 1968 was not followed up on!! You might
mention the scientific study discussed above.
In later studies DMSO was found to be a superb potentiator of
Adriamycin, Cisplatin, 5 Fluorouracil, and Methotrexate, and
others. For more information about DMSO and chemotherapy see the
excellent book (which talks about both IPT and DMSO being
combined with chemotherapy):
Treating Cancer With Insulin Potentiation Therapy, by Ross A.
Hauser, M.D. and Marion A. Hauser, M.S.
Absolutely nothing has been done about these discoveries for
almost 40 years!! The complete article discussing DMSO and
Haematoxylon can be found at:
The Original DMSO and Haematoxylon Journal Article
You might ask your oncologist why your chances of survival are
only 3% (ignoring all of their statistical gibberish such as
"5-year survival rates" and deceptive terms like "remission" and
"response"), when your chance of survival would be over 90% if
they used DMSO with very small doses of chemotherapy.
It would be better for medical doctors to treat cancer patients
with the right treatment than to have patients treat themselves
at home. Medical doctors can diagnose better, treat better,
watch for developing problems better, etc. Unfortunately,
doctors are using treatments that have been chosen solely on the
basis of their profitability rather than their effectiveness.
DMSO is a highly non-toxic, 100% natural product that comes
from the wood industry. But of course, like IPT, this discovery
was buried. DMSO, being a natural product, cannot be patented
and cannot be made profitable because it is produced by the ton
in the wood industry. The only side-effect of using DMSO in
humans is body odor (which varies from patient to patient).
The FDA took note of the effectiveness of DMSO at treating pain
and made it illegal for medical uses in order to protect the
profits of the aspirin companies (in those days aspirin was used
to treat arthritis). Thus, it must be sold today as a "solvent."
Few people can grasp the concept that government agencies are
organized for the sole purpose of being the "police force" of
large, corrupt corporations.
While it is generally believed that orthodox medicine and
modern corrupt politicians persecute alternative medicine, this
is not technically correct. What they do is persecute ANY cure
for cancer, it doesn't matter whether it is orthodox or
alternative. The proof of this is IPT and DMSO, which can both
be combined with chemotherapy. It appears that orthodox medicine
persecutes alternative medicine only because there are far more
alternative cancer treatments that can cure cancer than orthodox
Another substance that targets cancer cells is being researched
at Purdue University and other places: folic acid. This too will
be buried unless it can lead to MORE PROFITABLE cancer
But alternative medicine is not interested in combining DMSO
with chemotherapy. DMSO will combine with many substances, grab
them, and drag them into cancer cells. It will also blast
through the blood-brain barrier like it wasn't even there.
DMSO has been combined successfully with hydrogen peroxide
(e.g. see Donsbach), cesium chloride, MSM (though it may not
bind to MSM), and other products.
(Note: The issue has come up several times whether it would be
a good idea to mix DMSO with full-strength chemotherapy. This
question generally comes up when someone wants to take cesium
chloride and DMSO with their chemotherapy. The theory would lean
against such advice, however, in actual practice many patients
on chemotherapy have also taken DMSO. It does not seem to cause
a problem, but whether the DMSO binds to the chemotherapy would
depend on which chemotherapy was being used. DMSO does not bind
to every type of chemotherapy, only certain kinds (the exact
kinds are not totally known because the FDA forced all research
on DMSO to stop).
DMSO-The King Antioxidant
What It Does
DMSO tends to build up white blood cells and increase immune
production of MIF (migration inhibitory factors) of macrophages.
Thus, the immune system is made more effective by allowing
macrophages to move more quickly. Thus DMSO modulates
lymphocytes, and it therefore reactivates the production of MIF.
It also diminishes allergic reactions by unfolding the cell
membrane and making more cell receptor sites available to
attachment by specific antigens.
The modulating effect of DMSO on lymphocytes also tends to
increase the production of lymphokines (chemical immune cell
mediators) such as interferon. It potentiates cell mediated
immunity and can be effective in multiple sclerosis, systemic
lupus, erythematosus, rheumatoid arthritis, thyroiditis,
ulcerative colitis, cancer, etc.
What Are Its Major Therapeutic Properties?
* It blocks pain by interrupting conduction in the small
c-fibers, the non-myelinating nerve fibers.
* It is anti-inflammatory.
* It is anti bacterial, fungal and viral.
* It transports all molecules (drugs, etc.) across cell
* It reduces the incidence of platelet thrombi (clots in
* It effects cardiac contractility by inhibiting calcium to
reduce the workload of the heart.
* It is a vasodilator, probably related to histamine release in
the cells and to prostaglandin inhibition.
* It softens collagen.
* It is a scavenger of the hydroxyl free radical.
* It stimulates the immune system.
* It is a potent diuretic.
* It increases interferon formation.
* It stimulates wound healing.
DMSO has certain unique physiological characteristics which
stem from its molecular makeup:
* It is a simple small molecule with unusual properties.
* An exothermic reaction occurs when DMSO is diluted with water
(heat is generated).
* Hydroxyl radicals (OH), which are free radicals (oxidants),
are ubiquitous and highly injurious to cells—and thus health.
DMSO neutralizes (quenches) these free radicals. It is a free
* DMSO substitutes for water in the living cell—it can destroy
intracellular free radicals. No other antioxidant can do that.
* DMSO increases the permeability of cell membranes yielding a
flushing effect of toxins from intracellular location to
* It is an antidote to allergic reactions.
* It can penetrate any cell wall; thus it can get where most
* It has a very low index of any toxicity.
* Allergic reactions to DMSO can occur but they are uncommon.
* DMSO has a myriad of applications in medicine. Some are so
dramatically effective that the concept of such therapy just
boggles the mind!
Szmant, H. Harry. Physical properties of dimethyl sulfoxide and
its function in biological systems, Biological Actions of
Dimethyl Sulfoxide ed. by Stanley W. Jacob and Robert Herschler.
(New York: New York Academy of Sciences, 1975), pp. 20-23.
Barfeld, H., and T. Atoynatan. N-acetylcysteine inactivates
migration inhibitory factor and delayed hypersensitivity
reactions. Nature new Bio., 231:157-159, 1971.
Barfeld, H., and T. Atoynatan, Cytophilic nature of migration
inhibitory factor associated with delayed hypersensitivity,
Proc. Soc. Exp. Biol. Med., 139:497-501, 1969.
Tschope, M., cited in Raettig, H. “The potential of DMSO in
experimental immunology," Dimethylsulfoxyl, Internationales
Symposium in Wien. G. Laudahn and K. Getrich, eds.; 54.
Saladruck, Berlin, Germany, 1966.
Engel, M.F. Ann. N.Y. Acad. Sci., 141:638, 1967.
DMSO information : Hyperbaric Medicine : Melbourne - Australia
Itching is a common side effect of topical DMSO therapy - this
side effect can usually be avoided by diluting the concentration
of DMSO. ...
Dr. Stanley W. Jacob can be contacted at firstname.lastname@example.org. Dr.
Jacob is no longer seeing patients. He is taking this time to
write scientific publications and continue his research on DMSO.
Ultra Pure DMSO & MSM can be ordered directly from Dr.
Jacob's Laboratory. Contact Dr. Jacob's son, Jeff, by calling
toll free 1.866.375.2262 or visit www.jacoblab.com.
Pharmacology of DMSO
Stanley W. Jacob and Robert Herschler
Department of Surgery • Oregon Health Science University •
Portland, Oregon 97201
A wide range of primary pharmacological actions of dimethyl
sulfoxide (DMSO) has been documented in laboratory studies:
membrane transport, effects on connective tissue,
anti-inflammation, nerve blockade (analgesia), bacteriostasis,
diuresis, enhancements or reduction of the effectiveness of
other drugs, cholinesterase inhibition, nonspecific enhancement
of resistance to infection, vasodilation, muscle relaxation,
antagonism to platelet aggregation, and influence on serum
cholesterol in emperimental hypercholesterolemia. This substance
induces differntiation and function of leukemic and other
malignant cells. DMSO also has prophylactic radioprotective
properties and cryoprotective actions. It protects against
ischemic injury. (1986 Academic Press, Inc.)
The pharmacologic actions of dimethyl sulfoxide (DMSO) have
stimulated much research. The purpose of this report is to
summarize current concepts in this area.
When the theorectical basis of DMSO action is described, we can
list literally dozens of primary pharmacologic actions. This
relatively brief summary will touch on only a few:
(A) membrane penetration
(B) membrane transport
(C) effects on connective tissue
(E) nerve blockade (analgesia)
(H) enhancement or reduction of effectiveness
of other drugs
(I) cholinsterase inhibition
(J) nonspecific enhancement of resistance of
(L) muscle relaxation
(M) enhancement of cell differentiation and
(N) antagonism to platelet aggregation
(O) influence on serum cholesterol in
(P) radio-protective and cryoprotective
(Q) protection against ischemic injury
Primary Pharmocological Actions
A. Membrane Penetration
DMSO readily crosses most tissue membranes of lower animals and
Employing [35S] DMSO, Kolb et al,59 evaluated the absorption
and distribution of DMSO in lower animals and man. Ten minutes
after the cutaneous application in the rat, radioactivity was
measured in the blood. In man radioactivity appeared in the
blood 5 minutes after cutaneous application. One hour after
application of DMSO to the skin, radioactivity could be detected
in the bones.
Denko22 and his associates applied 35S-labeled DMSO to the skin
of rats. Within 2 hour a wide range of radioactivity was
distributed in all organs studied. The highest values occurred
in decreasing order in the following soft tissues; spleen,
stomach, lung, vitreous humor, thymus, brain, kidney, sclera,
colon, heart, skeletal muscle, skin, liver, aorta, adrenal, lens
of eye, and cartilage.
Rammler and Zaffaroni80 have reviewed the chemical properties
of DMSO and suggested that the rapid movement of this molecule
through the skin, a protein barrier, depends on a reversible
configurational change of the protein occurring when DMSO
substitutes for water.
B. Membrane Transport
Nonionized molecules of low molecular wight are transported
through the skin with DMSO. Substance of high molecular weight
such as insulin do not pass through the skin to any significant
extent. Studies in our laboratory have revealed that a 90%
concentration of DMSO is optimal for the passage of morphine
sulfate dissoved in DMSO.77 It would have been expected that
100% would provide better transport than 90%, and the reason for
an optimal effect at 90% DMSO remains unexplained. It is of
course well known that 70% alcohol has a higher phenol:water
partition coefficient than 100% alcohol.
Elfbaum and Laden27 conducted an in vitro skin penetration
study employing guinea pig skin as the membrane. They concluded
that the passage of picrate ion through this membrane in the
presence of DMSO was a passive diffusion process which adhered
to Fick's first law of diffusion. It is demonstrated by
diffusion and isotope studies that the absolute rate constant
for the penetration of DMSO was approximately 100 times greater
than that for the picrate ion. Thus, the two substances were
transferred through the skin independently of each other. The
exact mechanisms involved in the membrane penetrant action of
DMSO have yet to be elucidated.
Studies on membrane penetration and carrier effect have been
carrier effect have been carried out in agriculture, basic
biology, animals, and man. In field tests with severely diseased
fruit, Keil55 demonstrated that oxytetracycline satisfactorily
controlled bacterial spot in peaches. Control was significantly
enhanced by adding DMSO to the antibiotic spray. DMSO was
applied to 0.25 and 0.5% with 66 ppm of oxytetracycline. This
application gave control of the disease similar to that produced
alone by 132 ppm of oxytetracycline and suggested the
possibility of diluting the high-priced antibiotic with
relatively inexpensive DMSO. There is no good evidence in
animals that 0.5% DMSO has significant carrier effects. It could
well be that Keil's results were attributable to a carrier
effect, but the possibility should always be considered that
when DMSO is combined with another substance a new compound
results which can then exert a greater or lesser influence on a
Leonard63 studied different concentrations of several
water-soluable iron sources applied as foliage sprays to orange
and grapefruit trees whose leaves showed visible signs of iron
deficiency. The application of iron in DMSO as a spray was
followed by a rapid and extensive greening of the leaves, with a
higher concentration of chlorophyll.
Amstey and Parkman2 evaluated the influence of DMSO on the
infectivity of viral nucleic acid, an indication of its
transmembrane transport. It was found that DMSO enhanced polio
RNA infectivity in kidney cells from monkeys. Enhancement
occurred with all DMSO concentrations from 5 to 80% and was
optimal at 40% DMSO, with a 20-minute absorption period at room
temperature. A significant percentage of nucleic acid infection
was absorbed within the first 2 minutes.
Cochran and his associates14 concluded that concentrations of
DMSO below 20% did no influence the infectivity of tobacco
mosaic virus (TMV) or the viral RNA. With concentrations between
20 and 60% the infectivity of TMV and TMV RNA varied inversely
with the DMSO concentration.
Nadel and co-workers72 suggested that DMSO enhanced the
penetration of the infectious agent in experimental leukemia of
gunea pigs. Previously Schreck et al.97 had demonstrated that
DMSO was more toxic in vitro to lymphocytic leukemia than to
lymphocytes from normal patients.
Djan and Gunberg24 studied the percutaneous absorption of
17-estradiol dissolved in DMSO in the immature female rat. These
steroids were given in aqueous solutions subcutaneously or were
applied topically in DMSO. Vaginal and uterine weight increases
resulting from estrogen in DMSO administered topically were
comparable to results obtained in animals in which the drugs
were administered in pure form subcutaneously.
Smith102 reported that a mixture of DMSO and diptheria toxoid
applied frequently to the backs of rabbits causes a reduction of
the inflammation produced by the Shick test, indicating that a
partial immunity of diphtheria has been produced.
Finney and his associates29 studied the influence of DMSO and
DMSO-hydrogen peroxide on the pig myocardium after acute
coronary ligation with subsequent myocardial infaction. The
addition of DMSO to a hydrogen peroxide perfusion system
fascilitated the difffusion of oxygen into the ischemic
Maddock et al.66 designed experiments to determine the
usefulness of DMSO as a carrier for antitumor agents. The agents
were dissoved in 85-100% concentrations of DMSO. One of the
tumors studied was the L1210 leukemia. Survival time without
treatment was appoximately 8 days. The standard method of
employing Cytoxan intraperitoneally produced a survival time of
15.5 days. When Cytoxan was applied topically in water, the
survival time was 12.6 days, and topical Cytoxan dissolved in
DMSO resulted in survival time of 15.3 days.
Spruance recently studied DMSO as a vehicle for topical
antiviral agents, concluding that the penetration of acyclovir
(ACV) through guinea pigs skin in vitro was markedly greater
with DMSO than when ployethylene glycol (PEG) was the vehicle.
When 5% ACV in DMSO was compared with 5% ACV in PEG in the
treatmental herpes infection in the guinea pig, ACV DMSO was
The possibility of altering the blood-brain diffusion barrrier
with DMSO needs additional exploration. Brink and Stein10
employed [14C]pemoline dissolved in DMSO and injected
intraperitoneally into rats. It was found in larger amounts in
the brain than was a similar dose given in 0.3% tragacanth
suspension. The authors postulated that DMSO resulted in a
partial breakdown of the blood-brain diffusion barrier in vitro.
There is conflicting evidence as to whether dimethyl sulfoxide
can reversibly open the blood-brain barrier and augment brain
uptake of water-soluable compounds, including anticancer agents.
To investigate this, 125[-Human serum albumin, horse-radish
peroxidase, or the anticancer drug melphalan was administered iv
to rats or mice, either alone or in combination with DMSO. DMSO
administration did not significantly increase the brain uptake
of any of the compounds as compared to control uptakes. These
results do not support prior reports that DMSO increases the
permeability of water-soluable agents across the blood-brain
Maibach and Feldmann67 studied the percutaneous penetration of
hydrocortisone and testosterone in DMSO. The authors concluded
that there was a threefold increase in dermal penetration by
these steroids when they were dissolved in DMSO.
Sulzberger and his co-workers107 evaluated the penetration of
DMSO into human skin employing methylene blue, iodine, and iron
dyes as visual tracers. Biopsies showed that the stratum corneum
was completely stained with each tracer applied to the skin
surface in DMSO. There was little or no staining below this
layer. The authors concluded that DMSO carried substances
rapidly and deeply into the horny layer and suggested the
usefulness of DMSO as a vehicle for therapeutic agents in
inflammatory dermatoses and superficial skin infections such as
Perliman and Wolfe76 demonstrated that allergens of low
molecular weight such as penicillin G potassium, mixed in 90%
DMSO, were readily carried through intact human skin. Allergens
having molecular weights of 3000 or more dissolved in DMSO did
not penetrate human skin in these studies. On the other hand,
Smith and Hegre101 had previously recorded that antibodies to
bovine serum albumin developed when a mixture of DMSO and bovine
serum albumin was applied to the skin of rabbits.
Turco and Canada112 have studied the influence of DMSO on
lowering electrical skin resistance in man, In combination with
9% sodium chloride in distilled water, 40% DMSO decreased
resistance by 100%. It was postulated that DMSO in combination
with electrolytes reduced the electrical resistance of the skin
by facilitating the absorption of these electrolytes while it
was itself being absorbed.
DMSO in some instances will carry substances such as
hydrocortisone or hexachlorophene into the deeper layers of the
stratum corneum, producing a reservoir.104 This reservoir
remains for 16 days and resists depletion by washing of the skin
surface with soap, water, or alcohol.105
C. Effect on Collagen
Mayer and associates69 compared the effects of DMSO, DMSO with
cortisone acetate, cortisone acetate alone, and saline solutions
on the incidence of adhesions following vigorous serosal
abrasions of the terminal ileum of Wistar rats. Their technique
had developed adhesions in 100% of control animals in 35 days.
The treatments were administered daily as postoperative
intraperitoneal injections for 35 days. The incidence of
adhesions in different groups was DMSO alone: 20%,
DMSO-cortisone: 80%, cortisone alone: 100%, saline solution:
It has been observed in serial biopsy specimens taken from the
skin of patients with scleroderma that there is a dissolution of
collagen, the elastic fibers remaining intact.93 Gries et al.44
studied rabbit skin before and after 24 hour in vitro exposure
to 100% DMSO. After immersion in DMSO the collagen fraction
extractable with neutral salt solution was significantly
decreased. The authors recorded that topical DMSO in man exerted
a significant effect on the pathological deposition of collagen
in human postirradiation subcutaneous fibrosis but did not
appear to change the equilibrium of collagen metabolism in
normal tissue. Urinary hydroxyproline levels are increased in
scleroderma patients treated with topical DMSO.93 Keloids
biopsied in man before and after DMSO therapy show histological
improvement toward normalcy.28
Berliner and Ruhmann7 found that DMSO inhibited fibroblastic
proliferation in vitro. Ashley et al.3 reported that DMSO was
ineffective in edema following thermal burns of the limbs of
rabbits. Formanek and Kovak31 showed that topically applied DMSO
inhibited traumatic edema induced by intrapedal injection of
autologous blood in the leg of a rat.
DMSO showed no anti-inflammatory effect when studied in
experimental effect when studied in experimental inflammation
induced in the rabbit eye by mustard oil in the rat ear by
Gorog and Kovacs40 demonstrated that DMSO exerted minimal
anti-inflammation effects on edema induced by carrageenan. These
authors also studied the anti-inflammatory potential of DMSO in
adjuvant-induced polyarthritis of rats. Topical DMSO showed
potent anti-inflammatory properties in this model. Gorog and
Kovacs41 have also studied the anti-inflammatory activity of
topical DMSO, in contact dermatitis, allergic eczema, and
calcification of the skin of thr rat, using 70% DMSO to treat
the experimental inflammation. All these reactions were
The study of Weissmann et al.114 deserves mention in discussing
the anti-inflammatory effects of DMSO. Lysosomes can be
stabilized against a variety of injurious agents by cortisone,
and the concentration of the agent necessary to stabilize
lysosomes is reduced 10- to 1000-fold by DMSO. The possibility
was suggested that DMSO might render steroids more available to
their targets within tissues (membranes of cells or their
Suckert106 has demonstrated anti-inflammatory effects with
intra-articular DMSO in rabbits following the creation of
experimental [croton oil] arthritis.
E. Nerve Blockade (Analgesia)
Immersion of the sciatic nerve in 6% DMSO decreases the
conduction velocity by 40%. This effect is totally reversed by
washing the nerve in a buffer for 1 hour.89 Shealy99 studied
peripheral small fiber after-discharge in the cat.
Concentrations of 5-10% DMSO eliminated the activity of C fibers
with 1 minute: activity of the fibers returned after the DMSO
was washed away.
DMSO injected subcutaneously in 10% concentration into cats
produced a total loss of the central pain response. Two
milliliters of 50% DMSO injected into the cerebrospinal fluid
led to total anesthesia of the animal for 30 minutes. Complete
recovery of the animal occurred without apparent ill effect.100
Haigler concluded that DMSO is a drug that produced analgesia
by acting both locally and systemically. The analgesia appeared
to be unrelated to that produced by morphine although the two
appear to be a comparable magnitude. DMSO had a longer duration
of action than morphine, 6 hr vs 2 hr, respectively.45
DMSO exerts a marked inhibitory effect on a wide range of
bacteria and fungi including at least one parasite, at
concentrations (30-50%) likely to be encountered in
antimicrobial testing programs in industry.6
DMSO at 80% concentration inactivated viruses tested by Chan
and Gadenbusch. These viruses included four RNA viruses,
influenza A virus, influenza A-2 virus, Newcastle disease virus,
Semliki Forest virus, and DNA viruses.12
Seibert and co-worker98 studied the highly pleomorphic bacteria
regularly isolated from human tumors and leukemic blood. DMSO in
12.5-25% concentration caused complete inhibition of growth in
vitro of 27 such organisms without affecting the intact blood
Among the intriguing possibilities for the use of DMSO is its
ability to alter bacterial resistance. Pottz and associates78
presented evidence that the tubercle bacillus, resistant to
2000Ýg of treptomycin or isoniazide, became sensitive to 10Ýg of
either drug after pretreatment with 0.5-5% DMSO.
Kamiya et al.54 found that 5% DMSO restored and increased the
sensitivity of antibiotic-resistant strains of bacteria. In
particular, the sensitivity of all four strains of Pseudomonas
to colistin was restored when the medium contained 5% DMSO. The
authors recorded that antibiotics not effective against certain
bacteria, such as penicillin to E. coli, showed growth
inhibitory effects when the medium contained DMSO.
Ghajar and Harmon35 studied the influence of DMSO on the
permeability of Staphylococcus aureau, demonstrating that DMSO
increased the oxygen uptake but reduced the rate of glycine
transport. They could not define the exact mechanism by which
DMSO produced its bacteriostatic effect.
Gillchriest and Nelson37 have suggested that bacteriostasis
from DMSO occurs due to a loss of RNA conformational structure
required for protein synthesis.
Formanek and Suckert32 studied the diuretic effects of DMSO
administered topically to rats five times daily in a dosage of
0.5 ml of 90% DMSO per animal. The urine volume was increased
10-fold, and with the increase in urine volume, there was an
increase in sodium and potassium excretion.
H. Enhancement or Reduction of Concomitant Drug Action
Rosen and associates84 employed aqueous DMSO to alter the LD50
in rats and mice when oral quaternary ammonium salts were used
as test compounds. In rats, the toxicity of pentolinium tartrate
and hexamethonium bitartrate was increased by DMSO, while the
toxicity of hexamethonium iodide was decreased.
Male68 has shown that DMSO concentrations of upward to 10% lead
to a decided increase in the effectiveness of griseofulvin.
Melville and co-workers70 have studied the potentiating action
of DMSO on cardioactive glycosides in cats, including the fact
that DMSO potentiates the action of digitoxin. This effect,
however, does not appear to involve any change in the rate of
uptake (influx) or the rate of loss (efflux) of glycosides in
Sams et al.90 studied the effects of DMSO on skeletal, smooth,
and cardiac muscle, employing concentrations of 0.6-6%. DMSO
strikingly depressed the response of the diaphragm to both
direct (muscle) and indirect (nerve) electrical stimulation, and
caused spontaneous skeletal muscle fasciculations. DMSO
increased the response of the smooth muscle of the stomach to
both muscle and nerve stimulations. The vagal threshold was
lowered 50% by 6% DMSO. Cholinesterase inhibition could
reasonably explain fasciculations of skeletal muscle, increased
tone of smooth muscle, and the lower vagal threshold observed in
these experiments. In vitro assays show that 0.8-8% DMSO
inhibits bovine erythrocyte cholinesterase 16-18%.
J. Nonspecific Enhancement of Resistance
In a study of antigen-antibody reactions, Reattig81 showed that
DMSO did not disturb the immune response. In fact, the oral
administration of DMSO to mice for 10 days prior to an oral
infection with murine typhus produced a leukocytosis and
enhanced resistance to the bacterial infection.
Adamson and his co-workers1 applied DMSO to a 3-1 pedicle flap
raised on the back of rats. The anticipated slough was decreased
by 70%. The authors suggested that the primary action of DMSO on
pedicle flap circulation was to provoke a histamine-like
reponse. Roth87 has also evaluated the effects of DMSO on
pedicle flap blood flow and survival, concluding that DMSO does
indeed increase pedicle flap survival, but postulating that this
increase takes place by some mechanism other than augmentation
of perfusion. Kligman56, 57 had previously demonstrated that
DMSO possesses potent histamine-liberating properties.
Leon62 has studied the influence of DMSO on experimental
myocardial necrosis. DMSO therapy effected a distinct
modification with less myocardial fiber necrosis and reduced
residual myocardial fibrosis. The author reported that neither
myocardial rupture nor aneurysm occured in the group treated
L. Muscle Relaxation
DMSO applied topically to the skin of patients produces
electromyographic evidence of muscle relaxation 1 hour after
M. Antagonism to Platelet Aggregation
Deutsch23 has presented experimental data showing that 5% DMSO
lessons the adhesiveness of blood platelets in vitro. Gorog39
has shown that DMSO is a good antagonist to platelet aggregation
as well as thrombus formation in vivo. Gorog evaluated this in
the hamster cheek pouch model.
N. Enhancement of Cell Differentiation and Function
It has been shown that dimethyl sulfoxide induces
differentiation and function of leukemic cells of mouse 11, 33,
46, 65, 92, 115, rat,58 and human.9, 15, 16, 34, 109 DMSO was
also found to stimulate albumin production in malignantly
transformed hepatocytes of mouse and rat49 and to affect the
membrane-associated antigen, enzymes, and glycoproteins in human
rectal adenocarcinoma cells.111 Hydrocortisone-induced
keratinization of chick embryo cells74 and adriamcycin-induced
necrosis of rat skin108 were inhibited by DMSO.
Furthermore, modification by DMSO of the function of normal
cells has been reported. DMSO stimulates cyclic AMP accumulation
and lipolysis and decreases insulin-stimulated glucose oxidation
in free white fat cells of [the] rat. It also enhances heme
synthesis in quail embryo yolk sac cells.110
Leukemic blasts can be induced by external chemical agents to
mature to neutrophils, monocytes, or RBCs. The phenotype of
leukemic cells thus results from both internal genetic
aberrations and the response of leukemic cells to their external
environment. When human myeloid leukemia cells are exposed in
vitro to a variety of agents (e.g.vitamin A or dimenthyl
sulfoxide) the blasts lose their proliferative potential, the
expression of oncogene products is sharply decreased, and after
5 days the leukemic cells become morphologically mature and
functional neutrophils. Some patients with myeloid leukemias
have responded to therapy designed to induce maturation in vivo.
The induced maturation of leukemic cells is a new therapeutic
tactic-alternative to cytotoxic drug therapy-wherein leukemic
cells are destroyed by transforming them into neutrophils.86
O. Influence on Serum Cholesterol in Experimental
Rabbits given a high cholesterol diet with 1% DMSO showed
one-half as much hypercholesterolemia as control animals.48
P. Radioprotective and Cryoprotective Actions
M.J. Ashwood-Smith has written a comprehensive review of these
Q. Protection against Ischemic Injury
De la Torre has advanced a scheme based on both investigated
and theoretical actions of DMSO on the biochemical events
generated after an ischemic injury. He previously proposed this
hypothetical model to help conceptualize how DMSO, or similar
drugs, mights affect the pathochemical balance that results in
lack of tissue perfusion following trauma.19
The biochemical and vascular responses to injury appear to have
a cause and effect relationship that can be integrated in terms
of substances that either increase or decrease blood flow. The
substance's effect can be physical, i.e. reduce or increase the
vessel lumen obstruction, or chemical, i.e. reduce or increase
the vessel lumen diameter (vasoconstriction/vasodilation).
Platelets, for example, can induce both conditions. Obstruction
of the vessel lumen can result from platelet adhesion (platelet
buildup in damaged vessel lining) or platelet aggregation.
Platelet damage moreover can cause vasoconstriction or vasospasm
by liberating vasoactive substances locally with the blood
vessel or perivascularly, if penetrating damage to the vessel
has occurred. There are two storage sites within platelets that
contain most of these vasoactive substances. The alpha granules
contain fibrinogen, while the dense bodies store ATP, ADP,
serotonin, and calcium, which can be secreted by the platelet
into the circulation by a canalicular system.5 Thromboxane A2
has also been shown to be manufactured in the microsomal
fraction of animal and human platelets.73 All these vasoactive
substances (with the exception of ATP) can cause significant
reduction of blood flow by physical or chemical reactivity on
DMSO can antagonize a number of these vasoactive substances
released by the platelets, which could consequently induce
vasoconstriction, vasospasm, or obstruction of vessel lumen. For
example, a study has shown that DMSO can inhibit ADP and
thrombin-induced platelet aggregation in vitro.95 It may
presumable do this by increasing the evels of cAMP (a strong
platelet deaggregator) through inhibition of its degradative
enzyme, phosphodiesterase.26, 51 DMSO is reported to deaggregate
platelets in vivo following experimental cerebral ischemia.26,
51 This effect may be fundamental in view of the finding that
cerebral ischemia produces transient platelet abnormalities that
may promote microvascular aggregation formation and extend the
area of ischemic injury.25
The biochemical picture is further complicated by the possible
activity of DMSO on other vasoactive substances secreted by the
platelets during injury or ischemia. For example, the release of
calcium from cells from cells or platelets and its effect on
arteriolar-wall muscle spasm may be antagonized by circulating
DMSO.13, 88 Collagen-induced platelet release may also be
blocked by DMSO.44, 94
The following effects of DMSO are likely to be involved in its
ability to protect against ischemic injury.
DMSO and PGTX System
Little is known about the actions of DMSO on the prostanoids
(PG/TX). Studies have reported that DMSO can increase the
synthesis of PGE1, a moderate vasodilator.61. PGE1 can reduce
platelet aggregation by increasing cAMP levels and also inhibit
the calcium-induced release of noradrenalin in nerve terminals,
an affect that may antagonize vasoconstriction and reduction of
cerebral blood flow.53
DMSO, it will be recalled, also has a direct effect on cAMP. It
increases cAMP presumably by inhibiting phosphodiesterase,113
although an indirect action on PGI2-induced elevation of
platelet cAMP by DMSO should not be ruled out. Any process that
increases platelet cAMP will exert strong platelet
It has also been reported that DMSO can block PFG2 receptors
and reduce PFE2 synthesis.82 Both these compounds can cause
moderate platelet aggregation and PFG2 is known to induce
vasoconstriction.60 The effects of DMSO on thromboxane synthesis
are unknown. It could, however, inhibit TXA2, biosynthesis in
much the same way as hydralazine or dipyridamole42 since it
shares a number of similar properties with these agents:
specifically, their increase of cAMP levels.
DMSO and Cell Membrane Protection
The ability of DMSO to protect cell membrane integrity in
various injury models is well documented.38, 64, 91, 114
Cell membrane preservation by DMSO might help explain its
ability to improve cerebral and spinal cord blood flow after
injury.18 DMSO could be preventing impairment of cerebrovascular
endothelial surfaces where PGI2 is elaborated and where
platelets can accumulate following injury. The effects of DMSO
may be two-fold: reduction of platelet adhesion by collagen,44
and reduction of platelet adhesion by protecting the vascular
endothelium and ensuring PGI2 release.
DMSO, Hydroxyl Radicals, and Calcium
Although many hormones, chemical transmitters, peptides, and
numerous enzymes can be found in mammalian circulation at any
given time, it is the hydrozyl radicals that have drawn
attention by playing an important role in the pathogenesis of
ischemia.21, 30 Free radicals can be elaborated by peroxidation
of cellular membrane-bound lipids where oxygen delivery is not
totally abolished, as in ischemia and hypoxia, or when oxygen is
resupplied after an ischemic episode.83
One of the significant sites where hydroxyl radicals can form
following ischemia is in mitochondria. DMSO is known to be an
effective hydroxyl radical scavenger.4, 20, 75 Since it has been
shown that DMSO can improve mitochondrial oxidative
phosphorylation, it has been suggested that DMSO may act to
neutralize the cytotoxic effects of hydroxyl radicals in
mitochondria themselves.96 Oxidative phosphorylation is one of
the primary biochemical activities to be negatively affected
following ischemic injury. DMSO has also been reported to reduce
ATPase activity in submitochondrial particles,17, 36 an effect
that can lower oxygen utilization during cellular ischemia.
It has been proposed that DMSO may reduce the utilization of
oxygen by an inhibiting effect on mitochondrial function. In one
experiment the energy loss due to inhibition of oxidative
activity after brain tissue was perfused with DMSO was
compensated for by an increase in glycolysis.36
It seems probable that the neutralizing action of DMSO on
hydroxyl radical damage following injury could diminish the
negative outcome of ischemia. However the formation of hydroxyl
radicals is dependent on time and oxygen availability, but the
development of ischemia is immediate and its reversal may depend
on more prevalent subsystems such as the PG/TX and platelet
interactions. Maintaining the balance of these subsystems
appears more critical in predisposing the outcome of cerebral
Another interesting effect of DMSO is on calcium. When isolated
rat hearts are perfused with calcium-free solution followed by
reperfusion with a calcium-containing solution, a massive
release of creatine kinase (indicating cardiac injury) is
observed. This creatine kinase level increase is accompanied by
electrocardiographic (EKG) changes and ultrastructural cell
damage.50 DMSO has been reported to significantly reduce the
release of creatine kinase and prevent EKG and ultrastructural
changes if it is present during reperfusion of the isolated rat
heart with a calcium-containing solution.88 Moreover,
examination of the heart tissue by electron microscopy showed
that DMSO-treated preparations lacked the mitochondrial swelling
and contraction band formation otherwise induced by the reentry
of calcium.88 These findings are supported by another
investigation showing that DMSO can block calcium-induced
degeneration of isolated myocardial cells.13 This protective
effect by DMSO on myocardial tissue may be critical during
ischemic myocardial infarction when evolutionary EKG changes,
serum creates kinase levels are elevated, and myocardial
necrosis can develop rapidly.
DMSO2 is not an effective cryoprotective agent; however,
Herschler47 has recorded that DMSO (dimethyl sulfone) is a
natural source of biotransformable sulfur in plants and lower
animals. Jacob and Herschler have reported a number of unique
properties possessed by DMSO.52 Since DMSO is oxidized to DMSO2
in vivo, scientists should include DMSO as a control in basic
biologic studies on DMSO in plants and animals.
(a) Although the abbreviation "Me2SO" has been recommended for
chemists by the IUPAC, the abbreviation for dimethyl sulfoxide
most familiar to those concerned with its medicinal uses is
"DMSO." Consequently, this generic pharmacological name for
dimethyl sulfoxide will be employed throughout this paper.
(b) Supported in part by a grant from The Ronald J. Purer
Foundation. Presented at the Symposium Biological Effects of
Cryoprotective Agents at the Cryobiology Meeting, June 1985,
(c) Stanley W. Jacob, MD, Gerlinger Associate Professor of
Surgery and Surgical Research.
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Source: Received September 9, 1985. Accepted September 16, 1985
by the Academic Press, Inc. Printed 1985 (pp. 14-27). DMSO
Organization wishes to thank the Academic Press, Inc., for
allowing us to place this article on our World Wide Web site.
Academic Press retains all copyright. To copy any portion of
this article, please obtain permission from the publisher.
DMSO (Dimethylsulfoxide) Treatments in
Jack Blount, M.D., Ronald M. Davis, M.D., Ray Evers, M.D.,
Stanley Wallace Jacob, M.D., Pat McGrady, Sr., Efrain Olszewer,
M.D., Gus J. Prosch, Jr., M.D., Dr. Paul K. Pybus, Fuad C.
Sabbag, M.D., Roger Wyburn-Mason, M.D., Ph.D., Alan Rory Zapata,
M.D./Responsible editor/writer Anthony di Fabio.
... The 30 patients included in this study were regular
patients in our clinic and were evaluated three times in order
to see if it was possible to use the HLB test as a measuring
method of FR, as well as DMSO as an optimum antioxidant. The
results obtained are represented in Figure 1, where we find an
initial average FR measuring 30.6% of the patients included,
with an important and significant decrease of FR production
after DMSO administration, obtaining lower levels with an
average of 10.6%. That represents a 66% decrease in patients
before beginning the DMSO therapy, and keeping the patients in
monthly applications we obtained an average of 13.3% of FR
synthesis. That represents 52% decrease than the patients had in
the beginning, and 12% higher than patients after any DMSO
It is important to verify that the higher values were obtained
in patients with RA, and the lowest in patients with OA.
This study was done by: Centro Internacional de Medicina
Preventiva, Rua Compevas 211 Perdizes, Sao Paulo 1501. Brazil;
Tel: (011) 623000.
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The subject of DMSO therapy has its own web page on this site.
I want to focus here on its use in cancer therapy. DMSO has many
characteristics which make it a good adjunctive treatment for
cancer. Recall from our previous discussion that DMSO is a
super-solvent. It binds to water (which makes up around 65% of
the body) better than water does. This gives DMSO the ability to
penetrate every single cell of the body, so whatever its other
effects may be, they will be spread systemically through the
entire body. Whatever is administered with DMSO tends to bind
with the DMSO and is carried to the inside of cells along with
Animal studies show that DMSO, by itself, inhibits the growth
of breast, colon and bladder cancer, as well as leukemia, in
animals. The fact that this list is not longer probably reflects
the fact that DMSO has not been studied in other cancers.
If cytotoxic drugs are given to fight a cancer, they are more
effective when given with DMSO to escort them to the inside of
cancer cells. DMSO also relieves the pain of cancer and, by
being a free radical scavenger, reduces the side effects of
But, it's the old story! As with most effective and affordable
cancer therapies, it is not approved for that use by the FDA.
This, despite the presence of more than 6,000 articles attesting
to its safety and effectiveness and despite the fact that almost
every civilized country approves of DMSO treatment for cancer
except, you guessed it, the USA.
Nevertheless, some doctors do offer DMSO in the US. Because
DMSO is approved for one rare bladder condition called
"interstitial cystitis," it is possible for doctors to use it
for any other purpose. The FDA's authority extends to the
determination of whether or not an item is safe, and it is up to
the doctor to determine its correct use. While the FDA specifies
approval only for treatment of interstitial cystitis this
specification has no teeth.