title: Evaluation of dopaminergic and alpha adrenergic activities of TL-99 in peripheral tissues in vitro.
abstract: The dopaminergic and alpha adrenergic activities of TL-99 were investigated using in vitro preparations including cat right atria, guinea-pig atria, rat vas deferens and rabbit aortic strip. TL-99 was found to be as potent as clonidine as a stimulant of presynaptic alpha-2 adrenoceptors of noradrenaline nerve endings in guinea-pig atria and rat vas deferens. In the cat right atria, TL-99 preferently stimulates presynaptic dopamine receptors. The involvement of presynaptic alpha-2 adrenoceptor stimulation in TL-99-induced inhibition of tachycardic response to transmural stimulation in cat right atria is not clear. TL-99 is one thousand times less active as a stimulant of alpha-1 adrenoceptors of rabbit aorta than as a stimulant of presynaptic alpha-2 adrenoceptors of guinea-pig atria and rat deferens. Data from this manuscript as well as reports in the literature strongly suggest that TL-99 may interact with both alpha 2-adrenoceptors as well as dopamine receptors. The selectivity for receptor-type depends on test conditions, species variations and organ selectivity. The significance of these findings with TL-99 is discussed.
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology; D004347:Drug Interactions; D004558:Electric Stimulation; D006168:Guinea Pigs; D006220:Haloperidol / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009281:Naphthalenes / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011954:Receptors, Dopamine / Q000187:drug effects*; D013045:Species Specificity; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D014649:Vas Deferens / Q000187:drug effects
chemical_list: D009281:Naphthalenes; D011942:Receptors, Adrenergic, alpha; D011954:Receptors, Dopamine; D013764:Tetrahydronaphthalenes; C016893:2-(N,N-dimethylamino)-6,7-dihydroxytetralin; D006220:Haloperidol; D003000:Clonidine