Postsynaptic dopamine agonist properties of TL-99 are revealed by yohimbine co-treatment.
The claim that TL-99 (6,7-dihydroxy-2-dimethylaminotetralin hydrobromide) is a selective dopamine autoreceptor agonist relies partly upon indirect behavioral evidence, particularly the absence of stereotyped behavior in treated rats. The possibility was examined that concurrent alpha 2-adrenoceptor agonist properties of TL-99 could have masked postsynaptic dopamine agonist activity. Co-administration of yohimbine or piperoxan with a high dose of TL-99 (30 mg/kg) dramatically increased motor activity in reserpinized rats, whereas each drug by itself had no effect. Contralateral rotational behavior in 6-hydroxydopamine-lesioned rats resulted from combined treatment with yohimbine and a high dose of TL-99 (30 mg/kg) but appeared to be suppressed by concurrent flaccidity if TL-99 was given by itself. Yohimbine failed to alter the effects of 3-PPP (N-n-propyl-3-(3-hydroxyphenyl)-piperidine), another putative dopamine autoreceptor agonist, in either model of postsynaptic dopamine agonism. It is concluded that a concurrent behaviorally depressant action of TL-99, possibly alpha 2-agonism, masks the stimulation of postsynaptic dopamine receptors by high doses of TL-99.
D000818:Animals; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009281:Naphthalenes / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D011954:Receptors, Dopamine / Q000187:drug effects*; D012399:Rotation; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D015016:Yohimbine / Q000494:pharmacology*
D009281:Naphthalenes; D010880:Piperidines; D011942:Receptors, Adrenergic, alpha; D011954:Receptors, Dopamine; D013764:Tetrahydronaphthalenes; D015016:Yohimbine; C016893:2-(N,N-dimethylamino)-6,7-dihydroxytetralin; C026539:preclamol