Behavioural and convulsant actions of two methyl esters of beta-carboline-3-carboxylic acid in photosensitive baboons and in DBA/2 mice.
The proconvulsant and convulsant actions of methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) and of methyl-beta-carboline-3-carboxylate (beta-CCM) have been evaluated in two animal models of reflex epilepsy, the photosensitive baboon, Papio papio, and the audiogenic seizure prone DBA/2 mouse. In baboons, myoclonic responses to photic stimulation are markedly enhanced 1 min after DMCM, 0.25 mg/kg i.v. In the absence of photic stimulation DMCM, 0.5 mg/kg i.v. induces a single brief tonic clonic seizure within 10-90 s. beta-CCM, 0.025-0.05 mg/kg i.v. similarly enhances myoclonic responses to photic stimulation. Generalised seizures occur without photic stimulation 0.5-3 min after beta-CCM, 0.1-0.2 mg/kg. Pretreatment with the excitatory amino acid antagonist, 2-amino-7-phosphonoheptanoic acid (2-APH), 110 mg/kg i.v., prevents the generalised seizures induced by DMCM, 0.5 mg/kg, but not those induced by beta-CCM, 0.1-0.2 mg/kg. In DBA/2 mice beta-CCM and DMCM are indistinguishable in potency as convulsants (ED50 values for clonic seizures: 4.4 and 4.6 mg/kg i.p. respectively) and as proconvulsants (ED50 values for facilitation of clonic seizure responses to an 83 dB sound stimulus: 0.25 and 0.23 mg/kg). Pretreatment with 2-APH gives equipotent protection against audiogenic seizures induced by beta-CCM, 1 mg/kg or DMCM, 1 mg/kg. The differences in relative potency of beta-CCM and DMCM in the two species are probably accountable for in terms of differing metabolism. A differential action of the two beta-carbolines on receptor subtypes, with enhancement of excitatory amino acid release playing a more important role in epileptogenesis after DMCM, is proposed.
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives*; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D002243:Carbolines / Q000494:pharmacology*; D003292:Convulsants / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D010215:Papio; D010775:Photic Stimulation; D013045:Species Specificity; D013997:Time Factors
D000596:Amino Acids; D000927:Anticonvulsants; D002243:Carbolines; D003292:Convulsants; D007211:Indoles; C034818:methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate; D015763:2-Amino-5-phosphonovalerate; C036150:beta-carboline-3-carboxylic acid methyl ester; C031231:2-amino-7-phosphonoheptanoic acid