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Dimethyl Sulfoxide

The Elephant Formulary
© 2003-06 Susan K. Mikota DVM and Donald C. Plumb, Pharm.D.
Published by Elephant Care International -
www.elephantcare.org


Elephant specific information, if available, is in blue.

Chemistry - DMSO is a clear, colorless to straw-yellow liquid. It is dipolar, aprotic (acts as a Lewis base) and extremely hygroscopic. It has a melting/freezing point of 18.5°C, boiling point of 189°C, and a molecular weight of 78.1. It is miscible with water (heat is produced), alcohol, acetone, chloroform, ether and many organic solvents. A 2.15% solution in water is isotonic with serum.

 

Storage/Stability/Compatibility - Must be stored in airtight containers and away from light. As DMSO may react with some plastics, it should be stored in glass or in the container provided by the manufacturer. If DMSO is allowed to contact room air it will selfdilute to a concentration of 66-67%. DMSO is apparently compatible with many compounds, but because of the chances for accidental percutaneous absorption of potentially toxic compounds, the admixing of DMSO with other compounds is not to be done casually.

 

Pharmacology - The pharmacologic effects of DMSO are diverse. DMSO traps free radical hydroxide and its metabolite, dimethyl sulfide (DMS) traps free radical oxygen. It appears that these actions help to explain some of the anti-inflammatory, cryopreservative, antiischemic, and radioprotective qualities of DMSO.

 

DMSO will easily penetrate the skin. It also serves as a carrier agent in promoting the percutaneous absorption of other compounds (including drugs and toxins) that normally would not penetrate. Drugs such as insulin, heparin, phenylbutazone, and sulfonamides may all be absorbed systemically when mixed with DMSO and applied to the skin.

 

DMSO has weak antibacterial activity when used clinically and possible clinical efficacy when used topically as an antifungal. The mechanism for these antimicrobial effects have not been elucidated.

 

The anti-inflammatory/analgesic properties of DMSO have been thoroughly investigated. DMSO appears to be more effective an anti-inflammatory agent when used for acute in­flammation versus chronic inflammatory conditions. The analgesic effects of DMSO has been compared to that produced by narcotic analgesics and is efficacious for both acute and chronic musculoskeletal pain.

 

DMSO decreases platelet aggregation, but reports on its effects on coagulability have been conflicting, as has its effect on the myocardium. DMSO has diuretic activity independent of the method of administration. It also provokes histamine release from mast cells, which probably contributes to the local vasodilatory effects seen after topical administration.

 

DMSO also apparently has some anticholinesterase activity and enhances prostaglandin E, but blocks the synthesis of prostaglandins E2, F2-alpha, H2, and G2. It inhibits the enzyme alcohol dehydrogenase, which not only is responsible for the metabolism of alcohol, but also the metabolism of ethylene glycol into toxic metabolites.

 

Uses/Indications - Purported uses for DMSO are rampant, but the only FDA-approved veterinary indication for DMSO is: “...as a topical application to reduce acute swelling due to trauma” (Package Insert - Domoso®  — Syntex). Other possible indications for DMSO include: adjunctive treatment in transient ischemic conditions, CNS trauma and cerebral edema, skin ulcers/wounds/burns, adjunctive therapy in intestinal surgeries, and analgesia for post-operative or intractable pain, amyloidosis in dogs, reduction of mammary engorgement in the nursing bitch, enhancement of antibiotic penetration in mastitis in cattle, and limitation of tissue damage following extravasation injuries secondary to chemotherapeutic agents.

 

DMSO’s effect on alcohol dehydrogenase, may make it useful in the treatment of ethylene glycol poisoning, but this has not been sufficiently studied as of yet. DMSO’s attributes as a potential carrier of therapeutic agents across the skin and into the systemic circulation and its synergistic effects with other agents are potentially exciting, but require much more study before they can be routinely recommended.

 

While the potential indications for DMSO are many, unfortunately, the lack of well-controlled studies leave many more questions than answers regarding this drug.

 

Pharmacokinetics - DMSO is well absorbed after topical administration, especially at concentrations between 80-100%. It is extensively and rapidly distributed to virtually every area of the body. After IV administration to horses, the serum half-life was approximately 9 hours. DMSO is metabolized to dimethyl sulfide (DMS) and is primarily excreted by the kidneys, although biliary and respiratory excretion also takes place.

 

In cattle, the drug is eliminated quite rapidly and after 20 days no detectable drug or metabolites are found in milk, urine, blood, or tissues.

 

Contraindications/Precautions - Wear rubber gloves when applying topically, and apply with clean or sterile cotton to minimize the chances for contaminating with potentially harmful substances. Apply only to clean, dry areas to avoid carrying other chemicals into the systemic circulation.

 

DMSO may mask existing pathology with its anti-inflammatory and analgesic activity.

 

At high doses DMSO has been shown to be teratogenic in hamsters and chicks, but not in mice, rats or rabbits; weigh the risks versus benefits when using in pregnant animals.

 

Because DMSO may degranulate mast cells, animals with mastocytomas should only receive DMSO with extreme caution. DMSO should be used cautiously in animals suffering from dehydration or shock as its diuretic and peripheral vasodilatory effects may exacer­bate these conditions.

 

Adverse Effects/Warnings - When used as labeled, DMSO appears to be an extremely safe drug. Local effects (“burning”, erythema, vesiculation, dry skin, local allergic reactions) and garlic or oyster-like breath odor are the most likely adverse effects. They are transient and quickly resolve when therapy is discontinued. Lenticular changes, which may result in myopia, have been noted primarily in dogs and rabbits when DMSO is used chronically and at high doses. These effects are slowly reversible after the drug is discontinued.

 

When DMSO is administered intravenously to horses it may cause hemolysis and hemoglobinuria. These effects can be minimized by using concentrations of 20% or less (not less than 2% in water) and slowly administering.

 

Reports of hepatotoxicity and renal toxicity have also been reported for various species and dosages. These occur fairly rarely and some clinicians actually believe DMSO has a protective effect on ischemically insulted renal tissue.

 

Overdosage - The reported LD50’s following IV dosage in dogs and cats are: Cats ≈ 4 g/kg, and Dogs ≈ 2.5 g/kg. Signs of toxicity include: sedation and hematuria at non-lethal doses; coma, seizures, opisthotonus, dyspnea and pulmonary edema at higher dosages. Should an acute overdosage be encountered, treat supportively.

 

Drug Interactions - Because of its anticholinesterase activity, avoid the use of organophosphates or other cholinesterase inhibitors with DMSO. A fatality secondary to mercury intoxication was reported when DMSO was mixed with a mercury salt “red blister” and applied topically to the leg of a horse. Because it inhibits alcohol dehydrogenase, DMSO may prolong the effects of alcohol. Insulin, corticosteroids (including endogenous steroids), and atropine may be potentiated by DMSO.

 

Doses -

Horses:

a)   Liberal application should be administered topically to the skin over the affected area 2-3 times daily. Total daily dosage should not exceed 100 grams (or mls of liquid) and therapy should not exceed 30 days. (Package Insert - Domoso®; Syntex Animal Health)

b)   For treatment of cerebral edema secondary to eastern equine encephalitis (EEE): 1 g/kg as a 20% solution in D5W IV over 30 minutes once daily for up to 3 days. (Wilson 1987)

c)   Adjunctive treatment of equine protozoal myeloencephalitis (EPM): 1 g/kg as a 20% solution in D5W IV over 30 minutes once to twice daily. (Brewer 1987)

d)   For spinal cord injury: 1 gm/kg IV as a 20% solution in saline once daily for 3 days, then every other day for 6 days (Robinson 1987)

e)   For cantharidin poisoning: 0.9 gm/kg IV as a 10% solution in polyionic fluids (Schmitz and Reagor 1987)

f)    0.25 - 1.0 grams/kg diluted in normal saline or D5W at a concentration of not more than 20%. Concentrations greater than 10% should be given slowly IV.  Generally felt that the higher dosages are necessary to treat increased intracra­nial pressure and cerebral edema with twice daily dosing. At U of Minn. usual dose is 110 ml in 1 liter of saline (10%) given daily to an average sized horse. (Plumb 1988)

 

Monitoring Parameters -

1)   Efficacy

2)   Hemoglobinuria/hematocrit if indicated

3)   Ophthalmic exams with high doses or chronic use in the dog

 

Client Information/FDA Approval Status - Do not use non-medical grades of DMSO as they may contain harmful impurities. Wear rubber gloves when applying topically. DMSO should be applied with clean or sterile cotton to minimize the chances for contaminating with potentially harmful substances. Apply only to clean, dry skin. Use in well ventilated area; avoid inhalation and contact with eyes. May damage some fabrics. Keep lid tightly on container when not in use. Keep out of reach of children. Do not mix with any other substance without veterinarian’s approval.

 

Selected DMSO products are approved for use in dogs and in horses not intended for food purposes. It is a veterinary prescription (Rx) drug.

 

Dosage Forms/Preparations -

 

Veterinary Approved Products:

Dimethyl Sulfoxide Veterinary Gel 90%; Domoso® (Fort Dodge) Gel 90% (medical grade) in 60 g., and 120 g. tubes, and 425 g. jars.

 

Dimethyl Sulfoxide Veterinary Solution 90%; Domoso® (Fort Dodge) 90% (medical grade) in 4 oz spray bottle, 16 oz., and 1 gallon bottles

 

Human Approved Products:

Dimethylsulfoxide Solution 50 % aqueous solution in 50 mls and 70% solution in 250 mls; Rimso-50® (Research Industries) (Rx);Rimso-50® (Roberts);Kemsol® (Horner); (Rx)

 

Note: A topical otic product, Synotic®  (Fort Dodge) which contains: DMSO 60% and fluocinolone acetonide 0.01% is also available for veterinary use. Supplied in 8 ml and 60 ml dropper bottles.

 

For more information, refer to the excellent article reviewing DMSO by Brayton. (Brayton, CF. Dimethyl Sulfoxide (DMSO): A Review, Cornell Vet., 1986, 76; 61-90)

 

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