Indian Innovative Medicines Initiative
DMSO
Glibenclamide in DMSO IV for large hemorrhagic CVA to reduce brain swelling
Use of topical DMSO/with Diclofenac /Dexamethasone
MINOXIDIL+Dutasteride+cyproterone acetate topical for hair growth
Dimethylsulfoxide (DMSO) is a colorless organosulfur solvent, which dissolves both polar and non-polar compounds and is miscible in a wide range of organic solvents as well as in water.
From: Side Effects of Drugs Annual, 2012
Related terms:
Phosphate Chloride Potassium chloride Intravenous therapy Ethylenediaminetetraacetic acidAcetate HEPES Absorption (pharmacokinetics)EthanolAcetone
Learn more about Dimethyl sulfoxide
Laminitis
In Diagnosis and Management of Lameness in the Horse (Second Edition), 2011
Free Radical Scavengers
Dimethyl sulfoxide (DMSO) may be given intravenously for its free radical scavenging and antiinflammatory effects. DMSO (90% solution) mixed with polyionic solutions and 5% dextrose is best administered slowly at about 8 L/h. The concentration of DMSO must remain below 20% to avoid the risk of intravascular hemolysis. However, despite the potential value of DMSO, its promise as an effective laminitis therapy has not been fulfilled. Evidence exists that ischemia, reperfusion injury, and generation of free radicals are not involved in the pathogenesis of horses with laminitis induced with extract of Black walnut.18
Read full chapter
Systemic Inflammatory Response Syndrome
Elizabeth A. Carr, in Robinson's Current Therapy in Equine Medicine (Seventh Edition), 2015
Dimethylsulfoxide
Dimethylsulfoxide (DMSO) has been recommended as a treatment for endotoxemia and SIRS because of its antiinflammatory and reactive oxygen species (ROS)–scavenging benefits. Data on the benefits of DMSO administration in models of equine endotoxemia and reperfusion injury are lacking, but data in laboratory animals suggest that pretreatment with DMSO, before the onset of endotoxemia or ischemia-reperfusion injury, may be beneficial in decreasing cellular injury. The dosage recommendation for DMSO therapy is broad, ranging from 0.1 g/kg to 1 g/kg. DMSO should be diluted and infused as a 10% solution to avoid hemolysis.
Pharmacotherapy of joint and tendon disease
Carl A. Kirker-Head, Hillary Feldmann, in Equine Sports Medicine and Surgery (Second Edition), 2014
Effective dose
Domoso® (Pfizer Animal Health) is commercially available as a 90% DMSO veterinary gel for topical use. Manufacturer recommendations are for liberal application to skin over affected area 2–3 times per day. The total daily dosage is not to exceed 100 grams, and the duration of therapy is not to exceed 30 days. Domoso® (Pfizer Animal Health) is also available as a 90% veterinary solution. The recommended dose for the solution is 0.25–1.0 grams/kg diluted in saline or 5% dextrose solution at a concentration of not more than 10%. The 10% solution is to be given at a slow rate once daily for three days. The solution can be administered orally through a nasogastric tube at a dose of 1.0 grams/kg diluted in 1 liter of water.
Treatment protocosl for equine septic arthritis include the option of joint lavage with lactated Ringer's solution containing 5% to 40% DMSO. Lavage solutions containing DMSO concentrations in excess of 5% have been shown to have detrimental effects upon articular cartilage matrix metabolism. Until further investigation and pharmacokinetic studies can be performed, the concentration of DMSO contained within intra-articular lavage solutions should not exceed 5%.
The manufacturer cautions against the use of non-medical grade DMSO products, which may contain harmful impurities secondary to the distillation process. Washing of the hands and wearing protective rubber gloves before handling DMSO is strongly recommended in order to avoid transcutaneous penetration of potentially harmful substances.
Collection and processing of marrow and blood hematopoietic stem cells
Michele Cottler-Fox, ... John Theus, in Hematopoietic Stem Cell Transplantation in Clinical Practice, 2009
Addition of cryoprotectant
Dimethylsulfoxide (DMSO) is the cryoprotective agent most widely used to cryopreserve hematopoietic stem cells at present. DMSO is a universal solvent capable of stabilizing cell membranes under rapidly changing conditions, preventing intracellular ice crystal formation during freezing and heat release during the period of phase transition. DMSO has been described as toxic to stem cells at room temperature, for which reason investigators have emphasized the need to add it at 4°C to cells prior to controlled-rate freezing and to begin cryopreservation quickly thereafter. A final concentration of 10% DMSO with albumin or human serum is commonly used, with some centers using hydroxyethyl starch to help stabilize cell membranes and reduce the amount of DMSO used to 5%.
A new cryopreservative, Cryostor (BioLife Solutions Inc., Corning, NY), is also available. This compound modulates cellular biochemistry during the freezing process and is free of serum, proteins, and DMSO.
Painful Bladder Syndrome (Interstitial Cystitis)
Philip M. Hanno MD, MPH, in Penn Clinical Manual of Urology, 2007
INTRAVESICAL THERAPY
Dimethylsulfoxide (DMSO) is the only Food and Drug Administration (FDA)-approved medication for intravesical instillation for the treatment of PBS/IC. It is a product of the wood pulp industry and a derivative of lignin. It has exceptional solvent properties and is freely miscible with water, lipids, and organic agents. Pharmacologic properties include membrane penetration, enhanced drug absorption, anti-inflammatory, analgesic, collagen dissolution, muscle relaxant, and mast cell histamine release. Intravesical delivery by urethral catheter of 50 mL of a 50% solution (Rimso-50) allowed to remain in the bladder for 15 minutes and repeated at weekly intervals for 6 weeks is effective in ameliorating symptoms in about 60% of patients for a period of several months to over a year. Some patients who respond to an initial 6-week course are treated monthly for 6 months. Patients emit a garlic-like odor for several hours after treatment and may experience a short-term symptom exacerbation. It is often administered as part of a “cocktail” including 10 mg triamcinolone (Kenalog), 44 mEq sodium bicarbonate, and 40,000 units heparin.
Heparin, an exogenous glycosaminoglycan, can be administered intravesically in sterile water as a single agent. Forty thousand units in 20 mL of sterile water self-administered via catheter by the patients daily and held for 30–60 minutes has been reported beneficial, but no placebo-controlled studies have confirmed efficacy.
In a large multicenter randomized trial, intravesical bacille Calmette-Guérin (BCG) failed to show a statistically significant benefit compared to placebo. Capsaicin and resiniferatoxin, agents that desensitize C fiber afferent neurons, have failed to gain acceptance for intravesical therapy. The possible therapeutic value of intradetrusor injection of botulinum toxin type A is currently being determined in clinical trials. Older intravesical treatments such as chlorpactin, a derivative of bleach originally used to treat bladder tuberculosis, and silver nitrate are rarely used today for treatment of PBS/IC.
Disorders of the Gastrointestinal System
L. Chris Sanchez, in Equine Internal Medicine (Fourth Edition), 2018
Antioxidants
Dimethyl sulfoxide (DMSO) is used by some clinicians in an attempt to scavenge oxygen-derived radicals. However, DMSO failed to show beneficial effects in an experimental model of intestinal ischemia when administered on reperfusion of the ischemic intestine. DMSO at a dosage of 1 g/kg body mass increased mucosal loss after ischemia and reperfusion of the large colon, and a reduced dosage of 0.1 g/kg body mass has been proposed for horses with intestinal ischemia. DMSO failed to show significant benefit in an experimental model of endotoxemia in horses, although it ameliorated the effect on fever, and many clinicians do not advocate its use. The xanthine oxidase inhibitor allopurinol has been suggested as a treatment to prevent oxygen radical–induced tissue damage. During periods of ischemia tissue xanthine dehydrogenase is converted to xanthine oxidase, which on reperfusion catalyzes the generation of superoxide radicals. Evaluation in horses showed beneficial effects of allopurinol 5 mg/kg body mass administered 12 hours before endotoxin challenge. In another study mucosal damage attributable to oxygen-derived free radicals was not attenuated by allopurinol in an experimental ischemia–reperfusion model.
A worldwide yearly survey of new data in adverse drug reactions and interactions
N.H. Choulis, in Side Effects of Drugs Annual, 2012
Dimethylsulfoxide (DMSO) [SED-15, 1131; SEDA-32, 894; SEDA-33, 1015]
Dimethylsulfoxide (DMSO) is a colorless organosulfur solvent, which dissolves both polar and non-polar compounds and is miscible in a wide range of organic solvents as well as in water. It penetrates the skin very readily.
Umbilical cord blood transplantation using non-myeloablative conditioning is currently considered by many as a useful alternative for any patient who requires an unrelated donor allograft and who lacks a suitably matched and readily available volunteer. On the other hand, DMSO has been used for years as a cryoprotectant for umbilical cord blood; it acts by penetrating cells and binding water molecules and it has been described as harmless for the individual who receives it in limited amounts. DMSO-induced adverse reactions have been described in three cases and briefly reviewed; two of the three cases had a poor prognosis [27Ar].
In a review of the published literature, hundreds of adverse reactions, such as nausea, chills, cardiac dysrhythmias, neurological symptoms, and respiratory arrest, have been identified in association with the transplantation of stem cells cryopreserved with DMSO [28M]. These adverse reactions are generally accepted as commonplace, as most of them are transient, although some patients may require treatment.
Skin
A topical solution of diclofenac sodium in a vehicle containing dimethylsulfoxide has been studied in 793 subjects, mean age 63 years, with radiologically confirmed symptomatic osteoarthritis of the knees, who applied 40 drops qds for up to 1 year [29c]. They used the solution for an average of 204 days; 463 subjects used it for 6 months and 144 for 1 year. The most frequent adverse events were at the application site: dry skin (25%), contact dermatitis without vesicles (13%), or contact dermatitis with vesicles (9.5%); the risks did not increase with prolonged exposure. Skin irritation score was normal in 61% of the subjects: the scores were 0.5 (dryness or flaking) in 24%, 1 or 2 (erythema without or with induration) in 6.9%, and 3 or 4 (erythema with induration and vesicles/bullae) in 8.2%. Dropouts included 114 (14%) with an application site adverse event. There were individual laboratory test shifts towards abnormal for hemoglobin (3.2%), aspartate aminotransferase (6.4%), alanine aminotransferase (7.3%), and creatinine (4.2%), but few of the shifts were clinically significant. There were no increased risks of cardiovascular or cataract events.
Read full chapter
Topical and Transdermal Drug Delivery
S. Narasimha Murthy, H.N. Shivakumar, in Handbook of Non-Invasive Drug Delivery Systems, 2010
1.4.11.2 Sulfoxides and similar solvents
Dimethyl sulfoxide (DMSO) is a powerful aprotic solvent that is colorless, odorless, and hygroscopic. Studies have demonstrated that DMSO is effective in promoting the permeation of a number of hydrophilic and lipophilic permeants. It has been found to enhance the permeation of beta blockers (Kai et al., 1993) and ephedrine hydrochloride (Singh et al., 1993). The enhancer effect is reported to be concentration dependent, with concentrations greater than 60% required to show optimum efficacy (Williams and Barry, 2004). However, erythema and wheals of the stratum corneum have been reported at these relatively high concentrations of DMSO, which have also resulted in protein denaturation (Anigbogu et al., 1995). Human volunteer studies have demonstrated erythema, scaling, contact urticaria, stinging and burning sensations, and some systemic symptoms (Kligman, 1965). The skin penetration mechanisms of the aprotic solvents, and DMSO in particular, are complex. Upon application to human skin, DMSO is known to denature proteins and change the intracellular keratin conformation from helical to β sheet (Oertel, 1997). DMSO is said to interact with the head group of the lipid bilayers to distort the packing geometry. Further partitioning of the drug from the formulation into DMSO present within the tissue is favored.
Another aprotic solvent, dimethylformamide (DMF), is known to enhance absorption through the polar pathway by increasing diffusion and partitioning (Sinha and Kaur, 2000). A 12-fold increase in the flux of caffeine across DMF-treated human skin was observed, though the authors reported irreversible skin damage (Southwell and Barry, 1983). DMF is reported to increase the permeation of ephedrine hydrochloride across rat skin and human epidermis (Singh et al., 1993), and also promote the in vivo bioavailability of betamethasone-17-benzoate (Barry et al., 1984; Bennett et al., 1984).
Other aprotic solvents employed as permeation enhancers include dimethylacetamide, dimethyloctanamide, and dimethyldecanamide. Dimethylacetamide was found to increase the permeation of indomethacin from ointments and creams in rats (El-Faham and Safwat, 1992). Dimethyloctanamide and dimethyldecanamide were found to enhance the permeation of ibuprofen and naproxen from aqueous propylene glycol solutions across rat skin (Irwin et al., 1990). Decylmethylsulfoxide, a structural analog of DMSO, is known to act reversibly on human skin and promote the permeation of hydrophilic permeants (Williams and Barry, 2004). It is reported to increase the flux of oxymorphone hydrochloride through guinea-pig skin and human skin (Aungst et al., 1990a) and 5-fluorouracil across human skin (Goodmann and Barry, 1988).
Dimethyl Sulfoxide Toxicologic Problems
Patricia Talcott, in Equine Internal Medicine (Fourth Edition), 2018
Dimethyl Sulfoxide
Dimethyl sulfoxide (DMSO), a byproduct of the paper-making industry, is a colorless liquid originally used as an industrial solvent. The chemical is a polar compound that readily mixes with ethyl alcohol and many organic solvents; it is extremely hygroscopic and can absorb more than 70% of its weight of water from air. DMSO possesses some antimicrobial and antifungal activity, but its primary medical use has been as an antiinflammatory agent and a transdermal transport agent. More recently, DMSO has been used as a diuretic and has shown promising results when used to treat acute cranial and spinal cord trauma.
The systemic toxicity of DMSO is considered to be low, and its greatest toxic potential appears to result from its combination with other agents. However, in an experimental study rapid infusion of DMSO in 20% and 40% concentrations caused hemolysis, hemoglobinuria, diarrhea, muscle tremors, and signs of colic in some horses. The LD50 of DMSO has not been established for horses, but ranges between 2.5 and 9.0 g/kg as a single intravenous dose have been reported in a number of animal species. A dose of 1 g/kg intravenously has been suggested for use in horses. This dose should be diluted to a 10% to 20% solution and administered slowly intravenously.
DMSO produces hemolysis when given intravenously in concentrations of 20% to 50% or greater. If hemolysis is severe, affected horses may be at increased risk of developing hypoxic nephrosis. Concentrations of 10% or less are considered suitable for intravenous injection in horses. Additionally, increased white blood cell adherence and fibrinogen precipitation have been reported when concentrations greater than 50% were administered.
DMSO is a mild cholinesterase inhibitor, and its concurrent use with organophosphates or other cholinesterase inhibitors is not recommended. DMSO also is known to induce histamine release from mast cells, but the significance of this phenomenon is unclear.
Skin reactions to topically applied DMSO sometimes occur. Varying degrees of erythema, pruritus, drying, hardening, and desquamation of normal skin may be evident. These reactions are usually self-limiting and typically diminish with repeated applications.
The greatest risk of toxicity resulting from DMSO is probably a consequence of its concomitant use with other toxic or potentially toxic agents. DMSO may aid transport of a variety of toxic compounds across skin, thereby inducing toxicosis from the transported agent. For example, mercury toxicity has been reported in a horse that had a blister after DMSO and mercury were applied topically to a leg. In such instances, the clinician should treat the specific toxic reaction (or reactions) appropriately. No specific antidote is recognized for DMSO toxicosis, and it should always be used judiciously and conscientiously. The practitioner should heed the aforementioned precautions when administering the drug.
Globins and Other Nitric Oxide-Reactive Proteins, Part A
Paul R. Gardner, in Methods in Enzymology, 2008
10.1 Reagents
20 mM hemin prepared in dimethyl sulfoxide and stored at −20°
100 mM dithiothreitol in water stored at −20°
Dithionite (solid)
Tris‐Cl (50 mM), pH 8, containing EDTA (1 mM)
Catalase (bovine liver) (2,60,000 units per mL)
To reconstitute heme‐deficient flavohemoglobin with heme, flavohemoglobin is incubated with heme under reducing conditions in the presence of catalase to scavenge potentially damaging peroxide. Briefly, flavohemoglobin (0.5 to 0.75 mM) is prepared in a volume of 1.5 mL containing 50 mM Tris‐Cl, pH 8, 1 mM EDTA, 10 mM DTT, 3000 U of catalase, and hemin is then added slowly from a 20 mM stock in dimethyl sulfoxide to a final concentration of 0.5 mM. Dithionite (≈2 mg freshly dissolved in 25 μL of water) is added after 15 min of incubation to fully reduce hemin and eliminate O2. The reaction is incubated at 37° for 60 min. The flavohemoglobin is then immediately separated from free heme, catalase, and reductants by gel‐filtration chromatography. For this purpose, a 1.5 cm × 60 cm Superdex 200 column equilibrated with N2‐sparged 50 mM Tris‐Cl, pH 8, buffer containing 1 mM EDTA is used.
DMSO
Glibenclamide in DMSO IV for large hemorrhagic CVA to reduce brain swelling
Use of topical DMSO/with Diclofenac /Dexamethasone
MINOXIDIL+Dutasteride+cyproterone acetate topical for hair growth
Dimethylsulfoxide (DMSO) is a colorless organosulfur solvent, which dissolves both polar and non-polar compounds and is miscible in a wide range of organic solvents as well as in water.
From: Side Effects of Drugs Annual, 2012
Related terms:
Phosphate Chloride Potassium chloride Intravenous therapy Ethylenediaminetetraacetic acidAcetate HEPES Absorption (pharmacokinetics)EthanolAcetone
Learn more about Dimethyl sulfoxide
Laminitis
In Diagnosis and Management of Lameness in the Horse (Second Edition), 2011
Free Radical Scavengers
Dimethyl sulfoxide (DMSO) may be given intravenously for its free radical scavenging and antiinflammatory effects. DMSO (90% solution) mixed with polyionic solutions and 5% dextrose is best administered slowly at about 8 L/h. The concentration of DMSO must remain below 20% to avoid the risk of intravascular hemolysis. However, despite the potential value of DMSO, its promise as an effective laminitis therapy has not been fulfilled. Evidence exists that ischemia, reperfusion injury, and generation of free radicals are not involved in the pathogenesis of horses with laminitis induced with extract of Black walnut.18
Read full chapter
Systemic Inflammatory Response Syndrome
Elizabeth A. Carr, in Robinson's Current Therapy in Equine Medicine (Seventh Edition), 2015
Dimethylsulfoxide
Dimethylsulfoxide (DMSO) has been recommended as a treatment for endotoxemia and SIRS because of its antiinflammatory and reactive oxygen species (ROS)–scavenging benefits. Data on the benefits of DMSO administration in models of equine endotoxemia and reperfusion injury are lacking, but data in laboratory animals suggest that pretreatment with DMSO, before the onset of endotoxemia or ischemia-reperfusion injury, may be beneficial in decreasing cellular injury. The dosage recommendation for DMSO therapy is broad, ranging from 0.1 g/kg to 1 g/kg. DMSO should be diluted and infused as a 10% solution to avoid hemolysis.
Pharmacotherapy of joint and tendon disease
Carl A. Kirker-Head, Hillary Feldmann, in Equine Sports Medicine and Surgery (Second Edition), 2014
Effective dose
Domoso® (Pfizer Animal Health) is commercially available as a 90% DMSO veterinary gel for topical use. Manufacturer recommendations are for liberal application to skin over affected area 2–3 times per day. The total daily dosage is not to exceed 100 grams, and the duration of therapy is not to exceed 30 days. Domoso® (Pfizer Animal Health) is also available as a 90% veterinary solution. The recommended dose for the solution is 0.25–1.0 grams/kg diluted in saline or 5% dextrose solution at a concentration of not more than 10%. The 10% solution is to be given at a slow rate once daily for three days. The solution can be administered orally through a nasogastric tube at a dose of 1.0 grams/kg diluted in 1 liter of water.
Treatment protocosl for equine septic arthritis include the option of joint lavage with lactated Ringer's solution containing 5% to 40% DMSO. Lavage solutions containing DMSO concentrations in excess of 5% have been shown to have detrimental effects upon articular cartilage matrix metabolism. Until further investigation and pharmacokinetic studies can be performed, the concentration of DMSO contained within intra-articular lavage solutions should not exceed 5%.
The manufacturer cautions against the use of non-medical grade DMSO products, which may contain harmful impurities secondary to the distillation process. Washing of the hands and wearing protective rubber gloves before handling DMSO is strongly recommended in order to avoid transcutaneous penetration of potentially harmful substances.
Collection and processing of marrow and blood hematopoietic stem cells
Michele Cottler-Fox, ... John Theus, in Hematopoietic Stem Cell Transplantation in Clinical Practice, 2009
Addition of cryoprotectant
Dimethylsulfoxide (DMSO) is the cryoprotective agent most widely used to cryopreserve hematopoietic stem cells at present. DMSO is a universal solvent capable of stabilizing cell membranes under rapidly changing conditions, preventing intracellular ice crystal formation during freezing and heat release during the period of phase transition. DMSO has been described as toxic to stem cells at room temperature, for which reason investigators have emphasized the need to add it at 4°C to cells prior to controlled-rate freezing and to begin cryopreservation quickly thereafter. A final concentration of 10% DMSO with albumin or human serum is commonly used, with some centers using hydroxyethyl starch to help stabilize cell membranes and reduce the amount of DMSO used to 5%.
A new cryopreservative, Cryostor (BioLife Solutions Inc., Corning, NY), is also available. This compound modulates cellular biochemistry during the freezing process and is free of serum, proteins, and DMSO.
Painful Bladder Syndrome (Interstitial Cystitis)
Philip M. Hanno MD, MPH, in Penn Clinical Manual of Urology, 2007
INTRAVESICAL THERAPY
Dimethylsulfoxide (DMSO) is the only Food and Drug Administration (FDA)-approved medication for intravesical instillation for the treatment of PBS/IC. It is a product of the wood pulp industry and a derivative of lignin. It has exceptional solvent properties and is freely miscible with water, lipids, and organic agents. Pharmacologic properties include membrane penetration, enhanced drug absorption, anti-inflammatory, analgesic, collagen dissolution, muscle relaxant, and mast cell histamine release. Intravesical delivery by urethral catheter of 50 mL of a 50% solution (Rimso-50) allowed to remain in the bladder for 15 minutes and repeated at weekly intervals for 6 weeks is effective in ameliorating symptoms in about 60% of patients for a period of several months to over a year. Some patients who respond to an initial 6-week course are treated monthly for 6 months. Patients emit a garlic-like odor for several hours after treatment and may experience a short-term symptom exacerbation. It is often administered as part of a “cocktail” including 10 mg triamcinolone (Kenalog), 44 mEq sodium bicarbonate, and 40,000 units heparin.
Heparin, an exogenous glycosaminoglycan, can be administered intravesically in sterile water as a single agent. Forty thousand units in 20 mL of sterile water self-administered via catheter by the patients daily and held for 30–60 minutes has been reported beneficial, but no placebo-controlled studies have confirmed efficacy.
In a large multicenter randomized trial, intravesical bacille Calmette-Guérin (BCG) failed to show a statistically significant benefit compared to placebo. Capsaicin and resiniferatoxin, agents that desensitize C fiber afferent neurons, have failed to gain acceptance for intravesical therapy. The possible therapeutic value of intradetrusor injection of botulinum toxin type A is currently being determined in clinical trials. Older intravesical treatments such as chlorpactin, a derivative of bleach originally used to treat bladder tuberculosis, and silver nitrate are rarely used today for treatment of PBS/IC.
Disorders of the Gastrointestinal System
L. Chris Sanchez, in Equine Internal Medicine (Fourth Edition), 2018
Antioxidants
Dimethyl sulfoxide (DMSO) is used by some clinicians in an attempt to scavenge oxygen-derived radicals. However, DMSO failed to show beneficial effects in an experimental model of intestinal ischemia when administered on reperfusion of the ischemic intestine. DMSO at a dosage of 1 g/kg body mass increased mucosal loss after ischemia and reperfusion of the large colon, and a reduced dosage of 0.1 g/kg body mass has been proposed for horses with intestinal ischemia. DMSO failed to show significant benefit in an experimental model of endotoxemia in horses, although it ameliorated the effect on fever, and many clinicians do not advocate its use. The xanthine oxidase inhibitor allopurinol has been suggested as a treatment to prevent oxygen radical–induced tissue damage. During periods of ischemia tissue xanthine dehydrogenase is converted to xanthine oxidase, which on reperfusion catalyzes the generation of superoxide radicals. Evaluation in horses showed beneficial effects of allopurinol 5 mg/kg body mass administered 12 hours before endotoxin challenge. In another study mucosal damage attributable to oxygen-derived free radicals was not attenuated by allopurinol in an experimental ischemia–reperfusion model.
A worldwide yearly survey of new data in adverse drug reactions and interactions
N.H. Choulis, in Side Effects of Drugs Annual, 2012
Dimethylsulfoxide (DMSO) [SED-15, 1131; SEDA-32, 894; SEDA-33, 1015]
Dimethylsulfoxide (DMSO) is a colorless organosulfur solvent, which dissolves both polar and non-polar compounds and is miscible in a wide range of organic solvents as well as in water. It penetrates the skin very readily.
Umbilical cord blood transplantation using non-myeloablative conditioning is currently considered by many as a useful alternative for any patient who requires an unrelated donor allograft and who lacks a suitably matched and readily available volunteer. On the other hand, DMSO has been used for years as a cryoprotectant for umbilical cord blood; it acts by penetrating cells and binding water molecules and it has been described as harmless for the individual who receives it in limited amounts. DMSO-induced adverse reactions have been described in three cases and briefly reviewed; two of the three cases had a poor prognosis [27Ar].
In a review of the published literature, hundreds of adverse reactions, such as nausea, chills, cardiac dysrhythmias, neurological symptoms, and respiratory arrest, have been identified in association with the transplantation of stem cells cryopreserved with DMSO [28M]. These adverse reactions are generally accepted as commonplace, as most of them are transient, although some patients may require treatment.
Skin
A topical solution of diclofenac sodium in a vehicle containing dimethylsulfoxide has been studied in 793 subjects, mean age 63 years, with radiologically confirmed symptomatic osteoarthritis of the knees, who applied 40 drops qds for up to 1 year [29c]. They used the solution for an average of 204 days; 463 subjects used it for 6 months and 144 for 1 year. The most frequent adverse events were at the application site: dry skin (25%), contact dermatitis without vesicles (13%), or contact dermatitis with vesicles (9.5%); the risks did not increase with prolonged exposure. Skin irritation score was normal in 61% of the subjects: the scores were 0.5 (dryness or flaking) in 24%, 1 or 2 (erythema without or with induration) in 6.9%, and 3 or 4 (erythema with induration and vesicles/bullae) in 8.2%. Dropouts included 114 (14%) with an application site adverse event. There were individual laboratory test shifts towards abnormal for hemoglobin (3.2%), aspartate aminotransferase (6.4%), alanine aminotransferase (7.3%), and creatinine (4.2%), but few of the shifts were clinically significant. There were no increased risks of cardiovascular or cataract events.
Read full chapter
Topical and Transdermal Drug Delivery
S. Narasimha Murthy, H.N. Shivakumar, in Handbook of Non-Invasive Drug Delivery Systems, 2010
1.4.11.2 Sulfoxides and similar solvents
Dimethyl sulfoxide (DMSO) is a powerful aprotic solvent that is colorless, odorless, and hygroscopic. Studies have demonstrated that DMSO is effective in promoting the permeation of a number of hydrophilic and lipophilic permeants. It has been found to enhance the permeation of beta blockers (Kai et al., 1993) and ephedrine hydrochloride (Singh et al., 1993). The enhancer effect is reported to be concentration dependent, with concentrations greater than 60% required to show optimum efficacy (Williams and Barry, 2004). However, erythema and wheals of the stratum corneum have been reported at these relatively high concentrations of DMSO, which have also resulted in protein denaturation (Anigbogu et al., 1995). Human volunteer studies have demonstrated erythema, scaling, contact urticaria, stinging and burning sensations, and some systemic symptoms (Kligman, 1965). The skin penetration mechanisms of the aprotic solvents, and DMSO in particular, are complex. Upon application to human skin, DMSO is known to denature proteins and change the intracellular keratin conformation from helical to β sheet (Oertel, 1997). DMSO is said to interact with the head group of the lipid bilayers to distort the packing geometry. Further partitioning of the drug from the formulation into DMSO present within the tissue is favored.
Another aprotic solvent, dimethylformamide (DMF), is known to enhance absorption through the polar pathway by increasing diffusion and partitioning (Sinha and Kaur, 2000). A 12-fold increase in the flux of caffeine across DMF-treated human skin was observed, though the authors reported irreversible skin damage (Southwell and Barry, 1983). DMF is reported to increase the permeation of ephedrine hydrochloride across rat skin and human epidermis (Singh et al., 1993), and also promote the in vivo bioavailability of betamethasone-17-benzoate (Barry et al., 1984; Bennett et al., 1984).
Other aprotic solvents employed as permeation enhancers include dimethylacetamide, dimethyloctanamide, and dimethyldecanamide. Dimethylacetamide was found to increase the permeation of indomethacin from ointments and creams in rats (El-Faham and Safwat, 1992). Dimethyloctanamide and dimethyldecanamide were found to enhance the permeation of ibuprofen and naproxen from aqueous propylene glycol solutions across rat skin (Irwin et al., 1990). Decylmethylsulfoxide, a structural analog of DMSO, is known to act reversibly on human skin and promote the permeation of hydrophilic permeants (Williams and Barry, 2004). It is reported to increase the flux of oxymorphone hydrochloride through guinea-pig skin and human skin (Aungst et al., 1990a) and 5-fluorouracil across human skin (Goodmann and Barry, 1988).
Dimethyl Sulfoxide Toxicologic Problems
Patricia Talcott, in Equine Internal Medicine (Fourth Edition), 2018
Dimethyl Sulfoxide
Dimethyl sulfoxide (DMSO), a byproduct of the paper-making industry, is a colorless liquid originally used as an industrial solvent. The chemical is a polar compound that readily mixes with ethyl alcohol and many organic solvents; it is extremely hygroscopic and can absorb more than 70% of its weight of water from air. DMSO possesses some antimicrobial and antifungal activity, but its primary medical use has been as an antiinflammatory agent and a transdermal transport agent. More recently, DMSO has been used as a diuretic and has shown promising results when used to treat acute cranial and spinal cord trauma.
The systemic toxicity of DMSO is considered to be low, and its greatest toxic potential appears to result from its combination with other agents. However, in an experimental study rapid infusion of DMSO in 20% and 40% concentrations caused hemolysis, hemoglobinuria, diarrhea, muscle tremors, and signs of colic in some horses. The LD50 of DMSO has not been established for horses, but ranges between 2.5 and 9.0 g/kg as a single intravenous dose have been reported in a number of animal species. A dose of 1 g/kg intravenously has been suggested for use in horses. This dose should be diluted to a 10% to 20% solution and administered slowly intravenously.
DMSO produces hemolysis when given intravenously in concentrations of 20% to 50% or greater. If hemolysis is severe, affected horses may be at increased risk of developing hypoxic nephrosis. Concentrations of 10% or less are considered suitable for intravenous injection in horses. Additionally, increased white blood cell adherence and fibrinogen precipitation have been reported when concentrations greater than 50% were administered.
DMSO is a mild cholinesterase inhibitor, and its concurrent use with organophosphates or other cholinesterase inhibitors is not recommended. DMSO also is known to induce histamine release from mast cells, but the significance of this phenomenon is unclear.
Skin reactions to topically applied DMSO sometimes occur. Varying degrees of erythema, pruritus, drying, hardening, and desquamation of normal skin may be evident. These reactions are usually self-limiting and typically diminish with repeated applications.
The greatest risk of toxicity resulting from DMSO is probably a consequence of its concomitant use with other toxic or potentially toxic agents. DMSO may aid transport of a variety of toxic compounds across skin, thereby inducing toxicosis from the transported agent. For example, mercury toxicity has been reported in a horse that had a blister after DMSO and mercury were applied topically to a leg. In such instances, the clinician should treat the specific toxic reaction (or reactions) appropriately. No specific antidote is recognized for DMSO toxicosis, and it should always be used judiciously and conscientiously. The practitioner should heed the aforementioned precautions when administering the drug.
Globins and Other Nitric Oxide-Reactive Proteins, Part A
Paul R. Gardner, in Methods in Enzymology, 2008
10.1 Reagents
20 mM hemin prepared in dimethyl sulfoxide and stored at −20°
100 mM dithiothreitol in water stored at −20°
Dithionite (solid)
Tris‐Cl (50 mM), pH 8, containing EDTA (1 mM)
Catalase (bovine liver) (2,60,000 units per mL)
To reconstitute heme‐deficient flavohemoglobin with heme, flavohemoglobin is incubated with heme under reducing conditions in the presence of catalase to scavenge potentially damaging peroxide. Briefly, flavohemoglobin (0.5 to 0.75 mM) is prepared in a volume of 1.5 mL containing 50 mM Tris‐Cl, pH 8, 1 mM EDTA, 10 mM DTT, 3000 U of catalase, and hemin is then added slowly from a 20 mM stock in dimethyl sulfoxide to a final concentration of 0.5 mM. Dithionite (≈2 mg freshly dissolved in 25 μL of water) is added after 15 min of incubation to fully reduce hemin and eliminate O2. The reaction is incubated at 37° for 60 min. The flavohemoglobin is then immediately separated from free heme, catalase, and reductants by gel‐filtration chromatography. For this purpose, a 1.5 cm × 60 cm Superdex 200 column equilibrated with N2‐sparged 50 mM Tris‐Cl, pH 8, buffer containing 1 mM EDTA is used.
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