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.
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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.)
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Chemical References |
- Catecholamines
- Naphthalenes
- Receptors, Adrenergic
- Receptors, Dopamine
- Tetrahydronaphthalenes
- ADTN
- 2-amino-6,7-diacetoxy-1,2,3,4-tetrahydronaphthalene
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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)
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