Antiserotonin activity of 9-methyl-2-[3-(4-phenyl-1-piperazinylpropyl)]-1,2,3,4-tetrahydro -beta-carbolin-1-one (B-193)

Pol J Pharmacol Pharm. 1989 Mar-Apr;41(2):169-81.

Abstract

The effect of B-193 on the central and peripheral serotonin system was studied. B-193 antagonized the head-twitches responses induced by L-5-hydroxytryptophan (L-5-HTP) in mice (ED50 = 0.75 mg/kg ip and 6.6 mg/kg po) and lysergic acid diethylamide (LSD) in rats (ED50 = 1.54 mg/kg ip) and also counteracted forepaws clonic convulsions induced by tryptamine (ED50 = 3.07 mg/kg ip). B-193 (2.5-20 mg/kg ip) antagonized dose-dependently hyperthermia induced by fenfluramine or m-chlorophenylpiperazine (m-CPP) and in a dose of 1 mg/kg iv abolished the stimulation of the flexor reflex evoked by quipazine or fenfluramine. B-193 given in a concentration of 10(-7)-10(-5) mol/l competitively inhibited contractions of the rat stomach fundus strip induced by serotonin (5-HT) (pA2 = 6.5) and the increases in blood pressure induced by 5-HT in pithed rats (ED50 = 0.17 mg/kg iv). In receptor binding studies B-193 has shown distinct affinity to 5-HT2 receptors, and alpha 1-adrenoceptors much weaker affinity to 5-HT1 receptors and alpha 2-adrenoceptors but not to beta-adrenergic, GABA-ergic or benzodiazepine receptors. Our findings demonstrated that B-193 shows potent central and peripheral antiserotonin activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticonvulsants
  • Behavior, Animal / drug effects
  • Blood Pressure / drug effects
  • Body Temperature / drug effects
  • Carbolines / metabolism
  • Carbolines / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Male
  • Mice
  • Muscle Contraction / drug effects
  • Muscle, Smooth / drug effects
  • Piperazines / metabolism
  • Piperazines / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Receptors, Adrenergic, alpha / metabolism
  • Receptors, Adrenergic, beta / metabolism
  • Reflex / drug effects
  • Serotonin Antagonists / pharmacology*

Substances

  • Anticonvulsants
  • Carbolines
  • Piperazines
  • Receptors, Adrenergic, alpha
  • Receptors, Adrenergic, beta
  • Serotonin Antagonists
  • B 193