Interaction of the component enantiomers of the putative dopamine autoreceptor agonist, TL-99 (6,7-dihydroxy-2-dimethylamino tetralin) with dopaminergic systems in mammalian brain and teleost retina.
The enantiomers of the putative dopamine autoreceptor agonist, TL-99 (6,7-dihydroxy-2-dimethylaminotetralin) were examined in a number of in vivo and in vitro test paradigms to further examine the reported autoreceptor selectivity of this compound. The (+)-isomer of the aminotetralin was more active as a dopamine agonist than either the racemate or the (-)-enantiomer. In addition to this dopaminergic activity, TL-99 was found to be a potent alpha 2-adrenoceptor agonist, this activity being more prominent in the (+)-isomer. The (-)-isomer, however, was a weak alpha 2/DA receptor agonist and unlike the (+)-enantiomer was devoid of activity in the D-1-selective carp retina adenylate cyclase assay. Pharmacological examination of the effects of TL-99 on mouse locomotor activity showed that the effects of the aminotetralin in this dopamine autoreceptor test system were antagonized by either the alpha 2-antagonist, yohimbine or by the dopamine antagonist, sulpiride. TL-99 also produced contralateral turning in 6-OHDA lesioned rats. It is concluded that the apparent dopamine autoreceptor selectivity of TL-99 as assessed by in vivo animal test systems may be due partially to its alpha 2-agonist activity. The sedation and consequent reduction in mouse locomotor activity and in turning in the rat as the dose level is increased undoubtedly occurs via alpha 2-agonist and dopamine autoreceptor activity and cannot be interpreted as selectivity for the dopamine autoreceptor.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001921:Brain / Q000187:drug effects*; D005260:Female; D005399:Fishes; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009281:Naphthalenes / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D012160:Retina / Q000187:drug effects*; D013134:Spiperone / Q000494:pharmacology; D013237:Stereoisomerism; D013469:Sulpiride / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D009281:Naphthalenes; D011954:Receptors, Dopamine; D013764:Tetrahydronaphthalenes; D015016:Yohimbine; D013134:Spiperone; C016893:2-(N,N-dimethylamino)-6,7-dihydroxytetralin; D013469:Sulpiride; D001058:Apomorphine