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.