Catecholaminergic involvement in the biphasic effect of ADATN on temperature in mice.
A prodrug of 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (ADHTN), 2-amino-6,7-diacetoxy-1,2,3,4-tetrahydronaphthalene (ADATN), was tested for activation of central dopaminergic receptors as measured by colonic temperature in mice. Intraperitoneal injections of ADATN (200 and 800 mumol/kg) produced hypothermia; and intermediate dose (400 mumol/kg) caused hyperthermia followed by hypothermia. A similar biphasic effect occurred with the one dose of ADHTN (800 mumol/kg) tested. Pretreatments with catecholaminergic antagonists were used to characterize the biphasic effect of the intermediate dose of ADATN. The hyperthermic phase depended on the release of endogenous catecholamines which activated alpha- and beta-adrenergic receptors. The hypothermic phase was mediated by a direct activation of dopaminergic receptors. The results are discussed in terms of the pharmacodynamics of a prodrug, the actions of ADHTN, and the known effects of indirect- and direct-acting catecholaminergic agonists on temperature. The involvement of different catecholaminergic systems in the effects of ADATN may limit its usefulness as a dopaminergic prodrug.
D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D002395:Catecholamines / Q000378:metabolism / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D009281:Naphthalenes / Q000494:pharmacology*; D011941:Receptors, Adrenergic / Q000187:drug effects; D011954:Receptors, Dopamine / Q000187:drug effects; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D002395:Catecholamines; D009281:Naphthalenes; D011941:Receptors, Adrenergic; D011954:Receptors, Dopamine; D013764:Tetrahydronaphthalenes; C011639:ADTN; C030775:2-amino-6,7-diacetoxy-1,2,3,4-tetrahydronaphthalene