David E. McClure

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

SummaryThe enantiomers of the putative dopamine auto-receptor 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 α2-adrenoceptor agonist, this activity being more prominent in the (+)-isomer. The (−)-isomer, however, was a weak α2/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 α2-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 α2-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 α2-agonist and dopamine autoreceptor acitivity and cannot be interpreted as selectivity for the dopamine autoreceptor.