title: Effect of the beta-carboline abecarnil on spinal reflexes in mice and on muscle tone in genetically spastic rats: a comparison with diazepam.
abstract: Abecarnil is a beta-carboline agonist at benzodiazepine receptors with potent anxiolytic activity but no muscle relaxant side effects in rodents. Clinical experience suggests that changes in the muscle tone induced by benzodiazepines are related to their effects on spinal reflexes. The authors therefore analyzed the effect of treatment with abecarnil on spinal monosynaptic (Hoffmann reflexes) and polysynaptic (flexor) reflexes in mice and the influence of abecarnil on muscle tone in genetically spastic rats. The i.v. administration of abecarnil in mice (dose range, 0.02-1 mg/kg) depressed flexor reflexes in a dose-dependent manner; Hoffmann reflexes remained unchanged. Administration of diazepam i.v. (0.01-1 mg/kg) also reduced flexor reflexes and had little or no effect on Hoffmann reflexes. In genetically spastic rats, i.v. administration of abecarnil (10-30 mg/kg) decreased the muscle tone in a dose- and time-dependent manner. A similar muscle relaxant effect was observed in such rats after i.v. administration of diazepam (0.1-0.8 mg/kg). By contrast, i.p. administration of abecarnil in mice did not influence spinal reflexes up to the dose of 1 mg/kg and, in genetically spastic rats, did not affect muscle tone up to the dose of 100 mg/kg. Administration of diazepam i.p. (1 mg/kg) depressed flexor reflexes in mice and over the range 0.2 to 5 mg/kg produced a dose- and time-dependent decrease of muscle tone in genetically spastic rats. The muscle relaxant effect of i.p. diazepam could be antagonized by i.p. administered abecarnil. These studies thus demonstrate that i.v. but not i.p. administration of abecarnil may result in muscle relaxant action in mice and in genetically spastic rats.
authors.affiliation: Research Laboratories of Schering AG, Berlin, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Turski
authors.forename: D N
authors.initials: DN
authors.lastname: Stephens
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002243:Carbolines / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology*; D004195:Disease Models, Animal; D004576:Electromyography / Q000187:drug effects; D005260:Female; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009128:Muscle Spasticity / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D009129:Muscle Tonus / Q000187:drug effects* / Q000502:physiology; D010276:Parasympatholytics / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012018:Reflex / Q000187:drug effects* / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects* / Q000502:physiology*
chemical_list: D000927:Anticonvulsants; D002243:Carbolines; D010276:Parasympatholytics; C062769:abecarnil; D003975:Diazepam