Effects of methyl beta-carboline-3-carboxylate, Ro 15-1788 and CGS 8216 on muscle tone in genetically spastic rats.

Abstract

Genetically spastic rats were used for studying the effect on muscle tone of beta-carboline-3-carboxylic acid methylester (beta-CCM), an inverse benzodiazepine (BDZ) agonist, and that of Ro 15-1788 and CGS 8216, both putative antagonists of pharmacological actions of BDZs. These animals exhibit pathologically increased muscle tone, which can be recorded and quantified in the electromyogram (EMG) of the gastrocnemius (GS) muscle. beta-CCM, 2.5 and 3.0 mg/kg i.p., augmented the tonic activity in the EMG of GS muscle in spastic rats while it did not modify muscle tone at doses of 1.0 and 2.0 mg/kg. Diazepam, 0.4 mg/kg i.p., and Ro 15-1788, 5 mg/kg i.p., but not CGS 8216, 5 mg/kg i.p., antagonised the effect of the beta-carboline on muscle tone. Ro 15-1788, at doses of 0.1-5 mg/kg i.p., did not affect muscle tone in the genetically spastic rats, whilst at doses of 25-200 mg/kg the imidazodiazepine dose dependently increased the tonic activity in the EMG. The action of Ro 15-1788, 50 mg/kg i.p., was reversed by diazepam, 0.4 mg/kg i.p., and beta-CCM, 2 mg/kg i.p., while CGS 8216, 5 mg/kg i.p., facilitated the effect of Ro 15-1788 on muscle tone. CGS 8216 at doses of 5 and 25 mg/kg i.p. was devoid of any effect on muscle tone, whilst at doses of 50 and 200 mg/kg the pyrazoloquinoline increased the tonic activity recorded in the EMG from the GS muscle of the spastic rats.(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: C Ikonomidou, L Turski, T Klockgether, M Schwarz, K H Sontag
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 113 Issue 2 Pg. 205-13 (Jul 17 1985) ISSN: 0014-2999 [Print] Netherlands
• PMID: 2995064 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzodiazepinones
• Carbolines
• Pyrazoles
• Receptors, GABA-A
• Flumazenil
• 2-phenylpyrazolo(4,3-c)quinolin-3(5H)-one
• beta-carboline-3-carboxylic acid methyl ester

Topics

• Animals
• Benzodiazepinones (pharmacology)
• Carbolines (pharmacology)
• Dose-Response Relationship, Drug
• Electromyography
• Female
• Flumazenil
• Male
• Muscle Spasticity (physiopathology)
• Muscle Tonus (drug effects)
• Pyrazoles (pharmacology)
• Rats
• Rats, Mutant Strains
• Receptors, GABA-A (drug effects)