Use of potentiation of thyrotrophin releasing hormone (TRH)-induced hyperthermia as a test for screening antidepressants which activate alpha-adrenoceptor systems.
1 The minimal dose which significantly potentiates the hyperthermia induced by thyrotrophin releasing hormone (TRH, 40 mg/kg i.p.) in mice has been established for tricyclic and other antidepressants (imipramine, amitriptyline, clomipramine, nortriptyline, maprotiline, nomifensine, viloxazine) including a specific inhibitor of noradrenaline (NA) uptake (nisoxetine). 2 The minimal effective dose in this test has been compared with the minimal dose of the same compounds antagonizing reserpine-induced hypothermia. The ratio of the two doses for each substance indicates that potentiation of TRH-induced hyperthermia is, in general, the more sensitive test. 3 A correlation seems to exist between the alpha-adrenergic effect of antidepressants and the potentiation of TRH- induced hyperthermia. Those antidepressants which do not act on alpha-adrenergic systems (butriptyline, amineptine, trazodone, danitracen, fluoxetine) are inactive in this test. 4 This property may be used to select antidepressants that activate alpha-adrenoceptor systems.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001831:Body Temperature / Q000187:drug effects*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004357:Drug Synergism; D005260:Female; D051379:Mice; D012110:Reserpine / Q000037:antagonists & inhibitors; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*
D000316:Adrenergic alpha-Agonists; D000928:Antidepressive Agents; D013973:Thyrotropin-Releasing Hormone; D012110:Reserpine