2-Amino-6-trifluoromethoxy benzothiazole, a possible antagonist of excitatory amino acid neurotransmission--I. Anticonvulsant properties.
2-Amino-6-trifluoromethoxy benzothiazole (PK 26124) prevented convulsions induced in rodents by maximal electroshock, inhibitors of the synthesis of gamma-aminobutyric acid (GABA) and ouabain, but was inactive against seizures provoked by GABA antagonists, unlike diazepam, chlordiazepoxide, phenobarbital and valproic acid. 2-Amino-6-trifluoromethoxy benzothiazole prevented seizures induced by sound stimuli in DBA/2 mice (ED50 = 0.66; 2.1 and 4.1 mg/kg, i.p. according to the seizure component), postural seizures in El mice (ED50 = 7.5 mg, i.p.) and seizures induced by photic stimulation in the baboon, Papio papio, at 4 and 8 mg/kg (i.v.). This spectrum of anticonvulsant activity closely resembles that reported previously for dicarboxylic amino acid antagonists. Indeed, PK 26124 prevented seizures induced by L-glutamate (ED50 = 8.5 mg/kg, i.p.) or by kainate (ED50 = 9.25 mg/kg, i.p.) and tremors induced by harmaline (ED50 = 2.5 mg/kg, i.p.) In these tests diazepam was inactive (L-glutamate) or as potent as PK 26124 (kainate, harmaline), whereas it was 10-20 times more potent than PK 26124 against seizures induced by inhibitors of the synthesis of GABA. Together, these data suggest that PK 26124 possesses antagonistic properties of excitatory dicarboxylic amino acids, which may contribute to its anticonvulsant action.
D000596:Amino Acids / Q000037:antagonists & inhibitors*; D000818:Animals; D000927:Anticonvulsants; D001640:Bicuculline / Q000494:pharmacology; D004597:Electroshock; D005260:Female; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006246:Harmaline / Q000494:pharmacology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D010042:Ouabain / Q000494:pharmacology; D010215:Papio; D010433:Pentylenetetrazole / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D019782:Riluzole; D012640:Seizures / Q000139:chemically induced; D009435:Synaptic Transmission / Q000187:drug effects*; D013844:Thiazoles / Q000494:pharmacology*
D000596:Amino Acids; D000927:Anticonvulsants; D001640:Bicuculline; D005968:Glutamate Decarboxylase; D006246:Harmaline; D010042:Ouabain; D010433:Pentylenetetrazole; D010852:Picrotoxin; D019782:Riluzole; D013844:Thiazoles