Antiserotonin activity of 9-methyl-2-[3-(4-phenyl-1-piperazinylpropyl)]-1,2,3,4-tetrahydro -beta-carbolin-1-one (B-193).
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.
Wiczyńska
B
B
Institute of Pharmacology, Polish Academy of Sciences, Kraków.
Chojnacka-Wójcik
E
E
Rokosz-Pelc
A
A
Mazela
H
H
Przegaliński
E
E
D000818:Animals; D000927:Anticonvulsants; D001522:Behavior, Animal / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D002243:Carbolines / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010879:Piperazines / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D012018:Reflex / Q000187:drug effects; D012702:Serotonin Antagonists / Q000494:pharmacology*
D000927:Anticonvulsants; D002243:Carbolines; D010879:Piperazines; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D012702:Serotonin Antagonists; C062048:B 193