Catecholaminergic involvement in the biphasic effect of ADATN on temperature in mice.

Abstract

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.

• Authors: D J Dooley, M J Namkung, A A Hungar, A Horita, D M Bowden
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 71 Issue 2-3 Pg. 269-76 (May 08 1981) ISSN: 0014-2999 [Print] Netherlands
• PMID: 7250189 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Catecholamines
• Naphthalenes
• Receptors, Adrenergic
• Receptors, Dopamine
• Tetrahydronaphthalenes
• ADTN
• 2-amino-6,7-diacetoxy-1,2,3,4-tetrahydronaphthalene

Topics

• Animals
• Body Temperature (drug effects)
• Catecholamines (metabolism, physiology)
• Dose-Response Relationship, Drug
• Male
• Mice
• Naphthalenes (pharmacology)
• Receptors, Adrenergic (drug effects)
• Receptors, Dopamine (drug effects)
• Tetrahydronaphthalenes (pharmacology)