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Anticonvulsant effect of the selective 5-HT1B receptor agonist CP 94253 in mice.

Abstract
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.
AuthorsAnna Wesołowska, Agnieszka Nikiforuk, Ewa Chojnacka-Wójcik
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 541 Issue 1-2 Pg. 57-63 (Jul 10 2006) ISSN: 0014-2999 [Print] Netherlands
PMID16765343 (Publication Type: Journal Article)
Chemical References
  • Anticonvulsants
  • Benzamides
  • CP 94253
  • Indoles
  • N-(3-(2-dimethylamino)ethoxy-4-methoxyphenyl)-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)-(1,1'-biphenyl)-4-carboxamide
  • Oxadiazoles
  • Piperazines
  • Pyridines
  • Receptor, Serotonin, 5-HT1B
  • Serotonin 5-HT1 Receptor Agonists
  • Serotonin 5-HT1 Receptor Antagonists
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • Receptor, Serotonin, 5-HT1A
  • 5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole
  • Serotonin
  • N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
  • Diazepam
  • Fenclonine
  • Pentylenetetrazole
Topics
  • Animals
  • Anticonvulsants (pharmacology)
  • Benzamides (pharmacology)
  • Diazepam (pharmacology)
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Electroshock (adverse effects)
  • Fenclonine (pharmacology)
  • Indoles (pharmacology)
  • Male
  • Mice
  • Oxadiazoles (pharmacology)
  • Pentylenetetrazole (toxicity)
  • Piperazines (pharmacology)
  • Pyridines (pharmacology)
  • Receptor, Serotonin, 5-HT1A (physiology)
  • Receptor, Serotonin, 5-HT1B (physiology)
  • Seizures (etiology, physiopathology, prevention & control)
  • Serotonin (metabolism)
  • Serotonin 5-HT1 Receptor Agonists
  • Serotonin 5-HT1 Receptor Antagonists
  • Serotonin Antagonists (pharmacology)
  • Serotonin Receptor Agonists (pharmacology)

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