Alteration in ocular function induced by phenylethylamine analogs of dopamine

Dopamine (DA) and three methylated analogs (N-methyldopamine, NMDA; N, N- dimethyldopamine , DMDA ;N,N-di-n- propyldopamine , DPDA) were examined for effects on intraocular pressure (IOP) and pupil diameter (PD) in normal rabbits, sympathectomized (SX) rabbits and rabbits with transected extraocular muscles ( EOMX ) following topical administration. In normal rabbits, the predominant effect of DA, NMDA and DMDA was transient, unilateral ocular hypertension with minimal effects on PD. In contrast, DPDA produced bilateral ocular hypotension in normal rabbits. DA and NMDA did not produced ocular hypertension in EOMX rabbits indicative of an involvement of extraocular muscles in normal rabbits. In SX rabbits, NMDA produced mydriasis and exaggerated ocular hypertension followed by significant ocular hypotension; the ocular hypotensive phase was antagonized by timolol pretreatment. The ocular hypotensive activity of DPDA seen in normal rabbits was absent in SX rabbits suggestive of a neuronal site of action for DPDA. DPDA inhibited contraction of the cat nictitating membrane elicited by stimulation of pre- and postganglionic sympathetic nerves. This effect was antagonized by a dopamine (DA2) antagonist metoclopramide, indicative of a prejunctional site of action. NMDA and DA suppressed ocular hypertension induced by water loading. Only NMDA depressed the IOP recovery rate in response to infusion of hypertonic saline indicating suppression of aqueous humor formation. These results suggest that DA, NMDA and DMDA produce an initial ocular hypertension by contracting extraocular muscles. Timolol antagonized the ocular hypotensive effect of NMDA in SX rabbits indicating that this response is, in part, a function of beta-adrenoceptor stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)