Dopamine receptor stimulating activity of 5-hydroxy-6-methyl-2-aminotetralin derivatives

The effects of 5-hydroxy-6-methyl-2-aminotetralins were evaluated for central and presynaptic peripheral dopaminergic activity. Di-ethyl (DK-121) and di-propyl (DK-118) derivatives inhibited the tachycardia produced by postganglionic cardioaccelerator nerve stimulation in the cat. This effect was blocked by haloperidol (100 micrograms/kg). DK-118 inhibited stimulation-induced contraction of the cat nictitating membrane. The pressor response produced by lumbar sympathetic chain stimulation in the isolated hindlimb of the cat was inhibited by DK-118 following intravenous administration. Reflex sympathetic activation produced by 30 sec bilateral carotid occlusion was also inhibited by DK-118 in the dog. Centrally, DK-118 caused contralateral circling behavior in rats who had unilateral lesions of the caudate nucleus. DK-118 did not effect DOPA levels in either the caudate nucleus or olfactory tubercle. In contrast, DK-121 decreased DOPA levels in the caudate nucleus but did not produce circling behavior in rats. Both compounds have weak emetic activity in dogs. These results suggest that DK-121 and DK-118 possess stimulant properties on dopaminergic receptors in the central and peripheral nervous system. However, DK-121 does not appear to stimulate postsynaptic dopamine receptors in the central nervous system.