(+)-WIN 55,212-2, a novel cannabinoid receptor agonist, exerts antidystonic effects in mutant dystonic hamsters.
The effects of the novel high affinity cannabinoid receptor agonist (+)-WIN 55,212-2 ((R)-4,5-dihydro-2-methyl-4(4-morphoinylmethyl)-1-(1-naphthalen ylcarbonyl)-6H-pyrrolo[3,2,1-ij]quinolin-6-one) on severity of dystonia were investigated in mutant Syrian hamsters with primary generalized dystonia. Following injections of (+)-WIN 55,212-2 (1.0-5.0 mg/kg i.p.) a dose-dependent reduction of the severity of dystonia was observed. At antidystonic doses (2.5 and 5.0 mg/kg i.p.) (+)-WIN 55,212-2 caused a reduction of spontaneous motor activity and catalepsy. 1 mg/kg of (+)-WIN 55,212-2 exhibited neither antidystonic effects nor any side effects. However, the coadministration of 1.0 mg/kg (+)-WIN 55,212-2 with an ineffective dose of diazepam (0.1 mg/kg i.p.) exerted antidystonic effects in the absence of severe side effects. Although psychotropic effects of cannabinoids, such as (+)-WIN 55,212-2, limit the therapeutical utility of cannabinoids, the present data indicate that cannabinoids exert antidystonic effects and that low doses of cannabinoids may increase antidystonic efficacy of benzodiazepines.
Richter
A
A
Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, Hannover, Germany.
Löscher
W
W
D000700:Analgesics / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D048588:Benzoxazines; D006224:Cricetinae; D003975:Diazepam / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004421:Dystonia / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D007274:Injections, Intraperitoneal; D008297:Male; D008647:Mesocricetus; D009025:Morpholines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D009154:Mutation / Q000187:drug effects / Q000235:genetics; D009281:Naphthalenes / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism
D000700:Analgesics; D048588:Benzoxazines; D009025:Morpholines; D009281:Naphthalenes; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D003975:Diazepam