Anticonvulsant effect of the selective 5-HT1B receptor agonist CP 94253 in mice.
The effect of the selective 5-hydroxytryptamine1B (5-HT1B) receptor agonist 5-propoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-pyrrolo[3,2-b]pyridine (CP 94253) and the 5-HT1A/1B/1D receptor agonist 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridyl)-1H-indole (RU 24969) in maximal electroshock- and pentylenetetrazol-induced seizures in mice was examined. CP 94253 (10-40 mg/kg) afforded no protection against maximal electroshock-evoked convulsions, but produced anticonvulsant action in the pentylenetetrazol-induced seizures (ED50 = 29 mg/kg). The anticonvulsant effect of CP 94253 was abolished by the selective 5-HT1B receptor antagonist N-[3-(2-dimethylamino)ethoxy-4-methoxyphenyl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)-(1,1'-biphenyl)-4-carboxamide (SB 216641; 20 mg/kg) but it was maintained following the p-chlorophenylalanine (p-CPA; 3 x 300 mg/kg)-induced 5-HT depletion. Interestingly, CP 94253 potentiated the anticonvulsant activity of diazepam in the pentylenetetrazol test; on the other hand, the benzodiazepine receptor antagonist, flumazenil (10 mg/kg), did not modify the anticonvulsant effect of CP 94253. RU 24969 (5 mg/kg) evoked no effect in the maximal electroshock model, but it produced anticonvulsant activity in the pentylenetetrazol assay, the latter effect being attenuated by the selective 5-HT1A receptor antagonist N-(2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl)-N-(2-pyridyl)-cyclohexanecarboxamide (WAY 100635; 0.3 mg/kg) and SB 216641 (10-20 mg/kg). The obtained results suggest that CP 94253 exerts anticonvulsant activity on pentylenetetrazol-induced seizures in mice, as a consequence of stimulation of 5-HT1B receptors (probably located postsynaptically and/or as heteroreceptors); the antiseizure activity of RU 24969 seems to depend on the stimulation of both 5-HT1A and 5-HT1B receptors.
Wesołowska
Anna
A
Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, Kraków, PL 31-343, Poland.
Nikiforuk
Agnieszka
A
Chojnacka-Wójcik
Ewa
E
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004597:Electroshock / Q000009:adverse effects; D010134:Fenclonine / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D010069:Oxadiazoles / Q000494:pharmacology; D010433:Pentylenetetrazole / Q000633:toxicity; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology; D044302:Receptor, Serotonin, 5-HT1B / Q000502:physiology; D012640:Seizures / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D012701:Serotonin / Q000378:metabolism; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D000927:Anticonvulsants; D001549:Benzamides; C097067:CP 94253; D007211:Indoles; C108531:N-(3-(2-dimethylamino)ethoxy-4-methoxyphenyl)-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)-(1,1'-biphenyl)-4-carboxamide; D010069:Oxadiazoles; D010879:Piperazines; D011725:Pyridines; D044302:Receptor, Serotonin, 5-HT1B; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; C025145:5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole; D012701:Serotonin; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D003975:Diazepam; D010134:Fenclonine; D010433:Pentylenetetrazole