Inhibition of the binding and the behavioral effects of thyrotropin-releasing hormone (TRH) by the triazolobenzodiazepines.
The abilities of 4 triazolobenzodiazepines, adinazolam, alprazolam, estazolam and triazolam, to inhibit thyrotropin-releasing hormone (TRH) receptor binding and to antagonize the narcoleptic effects of TRH were examined. The IC50 values for inhibition of 3H-3-methyl-His-2-TRH (MeTRH) binding ranged from 19 microM to 477 microM, and the Hill coefficient from 0.53 to 0.98. Similar ranges of values were obtained from benzodiazepines of other structural classes. Thus, the inhibition of TRH receptor binding by the triazolobenzodiazepines is similar to that produced by other types of benzodiazepines. Furthermore, the triazolobenzodiazepine, alprazolam, antagonized the narcoleptic effect of TRH. However, this action is not necessarily linked to its inhibition of TRH receptor binding since alprazolam also inhibited the narcoleptic effect of amphetamine.
Kozlowski
M R
MR
Central Research Division, Pfizer Inc., Groton, CT 06340.
D000525:Alprazolam / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents; D001522:Behavior, Animal / Q000187:drug effects*; D001569:Benzodiazepines / Q000494:pharmacology*; D004949:Estazolam / Q000494:pharmacology; D066298:In Vitro Techniques; D051379:Mice; D010424:Pentobarbital / Q000037:antagonists & inhibitors; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D018025:Receptors, Thyrotropin-Releasing Hormone; D013973:Thyrotropin-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology; D014229:Triazolam / Q000494:pharmacology
D014151:Anti-Anxiety Agents; D017981:Receptors, Neurotransmitter; D018025:Receptors, Thyrotropin-Releasing Hormone; D001569:Benzodiazepines; D014229:Triazolam; D004949:Estazolam; D013973:Thyrotropin-Releasing Hormone; D010424:Pentobarbital; C039668:adinazolam; D000525:Alprazolam