Thyrotropin-releasing hormone (TRH) and its beta-alanine analogue: potentiation of the anticonvulsant potency of phenobarbital in mice.
Previous work has demonstrated that thyrotropin-releasing hormone (TRH) and its beta-alanine analogue (beta-ala TRH) are potent antagonists of barbiturate-induced sedation. This study sought to determine the effects of these oligopeptides on the anticonvulsant properties of phenobarbital in the maximal electroshock seizure (MES) test. Pro-leu-gly-NH2, another hypothalmic peptide was also examined. None of the peptides studied had any anticonvulsant properties of their own, but TRH and beta-ala TRH, though not pro-leu-gly-NH2, potentiated the anticonvulsant potency of phenobarbital. Thyrotropin (TSH) and tri-iodothyronine (T3) were in effective, suggesting that the effects observed with TRH are not mediated via the pituitary-thyroid axis. Since phenobarbital treatment of grand mal epilepsy is often limited by sedation and since TRH antogonizes sedation and enhances anticonvulsant effects of the barbiturate, the hormone or a congener may find value as an adjunct in therapy.
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D004357:Drug Synergism; D004597:Electroshock; D008297:Male; D051379:Mice; D010455:Peptides / Q000494:pharmacology; D010634:Phenobarbital / Q000494:pharmacology*; D012640:Seizures / Q000503:physiopathology; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000927:Anticonvulsants; D010455:Peptides; D013973:Thyrotropin-Releasing Hormone; D010634:Phenobarbital