Ocular hypotensive action of a dopaminergic (DA2) agonist, 2,10,11-trihydroxy-N-n-propylnoraporphine.

The dopamine (DA2) receptor agonist 2,10,11-trihydroxy-N-n-propylnoraporphine (TNPA) was tested for effects on 1) intraocular pressure (IOP), 2) aqueous humor flow rate, 3) electrically induced contractions of the cat nictitating membrane, 4) 3H-NE release from isolated rabbit iris-ciliary bodies and 5) cAMP accumulation in the isolated rabbit iris-ciliary body. Unilateral, topical administration of TNPA lowered IOP bilaterally in a dose-related fashion and inhibited the bilateral rise in IOP caused by water gavage. Topical pretreatment with metoclopramide, a DA antagonist, inhibited the ocular hypotensive response to TNPA. Subsequently, TNPA was shown to decrease aqueous humor inflow and IOP in normal rabbit eyes but not in surgically sympathectomized rabbit eyes. TNPA caused dose-dependent suppression of contractions of the cat nictitans, which was inhibited competitively by domperidone, a relatively selective DA2 receptor antagonist. In a test of prejunctional activity, TNPA caused dose-related inhibition of 3H-NE release from isolated, field-stimulated rabbit iris-ciliary bodies, which was inhibited by pretreatment with sulpiride, a relatively selective DA2 receptor antagonist. In a test of postjunctional activity, isoproterenol-stimulated cAMP accumulation in the isolated rabbit ciliary body was not affected by TNPA pretreatment. These results indicate that TNPA's suppressive action on aqueous humor flow rate and IOP is exerted predominantly on prejunctional (DA2) receptors of peripheral sympathetic nerves.