Alpha2-adrenergic inhibition of adenylate cyclase in bovine ciliary processes and rabbit iris ciliary body (ICB) was studied. With bovine ciliary process membrane, it was found that cAMP production in the presence of 1 uM isoproterenol was increased with increasing NaCl concentrations from 0 to 200 mM. Clonidine, an ct2-adrenergic agonist, produced a NaCl concentration-dependent inhibition of cAMP production in the presence of isoproterenol with a maximum inhibition at 200 mM NaCl (P<0.05). NaCl concentrations had no effect on basal adenylate cyclase activities and activity in the presence of clonidine alone. The cc2-adrenergic agonists, lofexidine, clonidine andp-amino-clonidine were tested for their ability to inhibit isoproterenol-stimulated adenylate cyclase in bovine ciliary process membrane in the presence of 200 mM NaCl. Their dose-response curves showed that they had similar IC50's but the maximum inhibition differed among these agonists. Clonidine was found to be apartial agonists producing 55% of the inhibition obtained with lofexidine. The specificity of inhibition of isoproterenol-stimulated adenylate cyclase by a2-agonists and blockade by pertussis toxin was examined by adenine labelling in rabbit ICB. The results demonstrate that cc2-adrenergic receptors exert specific inhibitory effects on adenylate cyclase activity in rabbit ICB, which are mediated by an inhibitory guanine nucleotide regulatory protein, Gi.

The present study examines the ocular hypotensive efficacy end pupillary response of the alpharadrenergic receptor agonists lofexidine and clonidine. The topical administration of lofexidine to rabbit eyes in concentrations ranging from 0.25 to 5%, produced a dosedependent bilateral reduction in intraocular pressure (IOP), with the contralateral (untreated) eye exhibiting a significantly greater reduction in IOP than the ipsilateral (treated) eye, particularly at the lower concentrations. The maximum decrease in IOP was observed at 60 min postdrug with the IOP recovering gradually to predrug values with time. Pupillary dilatation was observed only in the drug-treated eye. Unlike lofexidine, clonidine had no effect on pupillary diameter. Clonidine decreased IOP predominantly in the untreated contralateral eye at doses ranging from 0.625% to 5%, whereas a significant ocular hypertensive effect of clonidine was noted at the 7.5% dose in the treated ipsilateral eye. The present data provide evidence that topically administered lofexidine lowers IOP in normotensive New Zealand White (NZW) rabbits.