Cat Nictitating Membrane Research Articles

Modification by a tricyclic series of compounds of the noradrenaline effect on the cat nictitating membrane.

Journal Article Modification by a tricyclic series of compounds of the noradrenaline effect on the cat nictitating membrane Get access Gillian Sturman Gillian Sturman Research Laboratories, May & Baker Ltd., Dagenham, Essex, UK Search for other works by this author on: Oxford Academic Google Scholar Journal of Pharmacy and Pharmacology, Volume 23, Issue 2, February 1971, Pages 142–143, https://doi.org/10.1111/j.2042-7158.1971.tb08631.x Published: 12 April 2011 Article history Received: 02 November 1970 Published: 12 April 2011

Dual actions of some N-(1-phenylethyl)guanidines on the nictitating membrane of conscious cats

Abstract After 6 hr, high doses (10 or 20 mg/kg) of some adrenergic neuron blocking drugs derived from N-(1-phenylethyl)guanidine produce relaxation of the nictitating membranes of conscious cats which is less than that produced by small doses (2.5 or 5 mg/kg). After 24 hr, there were marked responses to some drugs that had produced little effect after 6 hr. High doses of the drugs contract the nictitating membranes of cats treated with pempidine or (—)-N-(1-phenylethyl)guanidine; low doses do not. This contraction opposes the relaxation evoked by the adrenergic neuron blockade and could account for the anomalous dose-response relationships. The contraction may result from localized release of noradrenaline from the nictitating membrane.

Dextromethorphan-monoamine oxidase inhibitor interaction in rabbits.

Abstract Severe toxic reactions may occur clinically when imipramine, pethidine or dextromethorphan is administered to a patient being treated with a monoamine oxidase inhibitor (MAOI). Previous reports indicate that imipramine or pethidine produces symptoms characterized by motor restlessness, tremor, extreme hyperpyrexia and death when administered to phenelzine-pretreated rabbits. The present study shows that dextromethorphan (5 mg kg−1) produces identical symptoms in rabbits pretreated with phenelzine sulphate (30 mg kg−1) or nialamide HCl (50 mg kg−1) 42 and 18 h before temperature recording. The dextromethorphan-MAOI interaction appears to be due to a 5-hydroxytryptamine potentiation. In the unanaesthetized cat nictitating membrane preparation, dextromethorphan (5 mg kg−1) markedly enhanced the response of noradrenaline and 5-HT but antagonized the effects of tyramine. This suggests that dextromethorphan blocks the uptake of these amines in the adrenergic nerve endings.

THE EFFECTS OF BLOCKING AGENTS UPON THE ISOLATED VAS DEFERENS OF THE GUINEA-PIG STIMULATED BY THE HYPOGASTRIC NERVE.

Abstract When the guinea-pig isolated vas deferens preparation was stimulated by its hypogastric nerve, the responses obtained at different frequencies of stimulation were all reduced proportionately by guanethidine, bretylium, reserpine and pentamethonium. The difference between guanethidine and bretylium in affecting the responses to nervous stimulation at different frequencies of the cat nictitating membrane reported by Boura & Green was not observed with this preparation. Papaverine reduced responses to high frequencies of stimulation more than those to low frequencies. Amphetamine also reduced responses to all frequencies uniformly except in the smallest doses used, which potentiated the responses to high frequencies; these doses reversed the reduction in response by guanethidine, bretylium and reserpine. Preparations stimulated between parallel electrodes responded similarly to those stimulated by the hypogastric nerve.

Antihypertensive effect of 3,3,5,5-tetramethyl-4-piperidone, a new compound extracted from Marasmius androsaceus

Aim of the study To evaluate the antihypertensive effect of 3,3,5,5-tetramethyl-4-piperidone (TMP), a new compound extracted from Marasmius androsaceus. Besides, the hemodynamic profiles and pertinent mechanism of the compound were explored. Materials and methods Acute and chronic antihypertensive effects of TMP were examined in spontaneous hypertensive rats (SHRs) and reno-hypertensive rats (two kidneys one clip model, 2K1C). Anesthetized dogs were used to evaluate the hemodynamic effects of TMP. Moreover, the cat nictitating membrane response was used to test the ganglionic blocking property of TMP. Results TMP (2.5, 5 and 10 mg/kg, p.o.) notably reduced the blood pressure of SHR in 30 min. Two-week administration of TMP (2.5, 5 and 10 mg/kg, p.o.) also decreased the blood pressure of 2K1C rats. TMP (30 mg/kg, i.v.) abolished the response of the nictitating membrane induced by preganglionic stimulation. The results of hemodynamic study in anesthetized dogs showed that, except for the reduction in blood pressure and left ventricular work, no other changes were detected. The results of heart rate variability analysis indicated an intact sympathetic–vagal balance after TMP treatment. Conclusions TMP is a new antihypertensive compound, and the effect is partially related to ganglionic blocking.

Purinergic cotransmission

Adenosine 5'-triphosphate (ATP) is a cotransmitter with classical transmitters in most nerves in the peripheral and central nervous systems, although the proportions vary between tissues and species and in different developmental and pathophysiological circumstances. There was early evidence that ATP was released together with acetylcholine (ACh) from motor nerves supplying skeletal muscle, although it was considered at the time as a molecule involved in the vesicular uptake and storage of ACh. Later it was shown that in the developing neuromuscular junction, released ATP acted on P2X receptor ion channels as a genuine cotransmitter with ACh. Adenosine triphosphate was shown to be released from sympathetic nerves supplying the guinea-pig taenia coli in 1971. Soon after, the possibility was raised that ATP was coreleased with noradrenaline from sympathetic nerves to guinea-pig seminal vesicle, cat nictitating membrane and guinea-pig vas deferens. Sympathetic purinergic cotransmission has also been demonstrated in many blood vessels. Parasympathetic nerves supplying the urinary bladder use ACh and ATP as cotransmitters; ATP acts through P2X ionotropic receptors, whereas the slower component of the response is mediated by the metabotropic muscarinic receptor. Adenosine triphosphate and glutamate appear to be cotransmitters in primary afferent sensory neurons. Adenosine triphosphate, calcitonin gene-related peptide and substance P coexist in some sensory-motor nerves. A subpopulation of intramural enteric nerves provides non-adrenergic, non-cholinergic inhibitory innervation of gut smooth muscle. Three cotransmitters are involved, namely ATP, nitric oxide and vasoactive intestinal polypeptide. In recent years, studies have shown that ATP is released with ACh, noradrenaline, glutamate, gamma-aminobutyric acid, 5-hyroxytryptamine and dopamine in different subpopulations of neurons in the central nervous system.

Pharmacological evidence of a role for prejunctionalimidazoline (I1) receptors in ocular function

Imidazoline and guanidiniun-substituted isoindoline compounds have been reported to demonstrate affinity for the putative imidazoline receptors (I 1) and alpha-2 (a 2) adrenoceptors. The purpose of this study was to determine the relative contribution of I 1 receptors to ocular actions of moxonidine (MOX) and brimonidine (BRIM) by utilizing relatively selective a 2 and I 1 antagonists. MOX, an a 2 /I 1 receptor agonist, BRIM, a selective a 2 agonist, efaroxan (EFA), an I 1 /a 2 antagonist and rauwolscine (RAU), a relatively selective a 2 antagonist, were utilized to study alterations in sympathetically evoked contractions of the cat nictitating membrane (CNM). MOX (1-10 µg) suppressed, dose dependently, contractions of the CNM elicited by electrically stimulating the cervical preganglionic sympathetic trunk. The suppressive effect of MOX was antagonized more effectively by EFA (333 µg) than by rauwolscine (333 µg). In contrast, RAU, but not EFA, completely reversed the suppressive effects of BRIM on electrically induced contractions of the CNM. In conclusion, these in vivo data suggest that I 1 receptors are involved in the pre-junctional (neuronal) modulation of contractions in the CNM (Supported by NIH grant EY06338).

Lisuride Acts at Multiple Sites to Induce Ocular Hypotension and Mydriasis

Topically unilaterally applied lisuride caused dose-related lowering of intraocular pressure in ipsilateral (treated) but not in contralateral eyes of normal rabbits. The ocular hypotensive response induced by lisuride was antagonized by pretreatment with metoclopramide, a dopamine receptor antagonist, and was partially reduced by local sympathetic denervation. In contrast to the unilateral effect on intraocular pressure, lisuride caused mydriasis in both eyes. Mydriasis was of greater magnitude and more sustained in normal eyes compared to sympathetically denervated eyes. Additional in vivo experiments demonstrated that lisuride caused dose-related suppression of neuronally initiated contractions of cat nictitating membrane. In in vitro experiments lisuride caused dose-related inhibition of norepinephrine release from isolated rabbit iris-ciliary bodies. Pretreatment with Bay K 8644, a calcium channel activator, did not attenuate lisuride-induced inhibition of norepinephrine release in isolated rabbit iris-ciliary bodies. Because lisuride pretreatment caused no change in isoproterenol-stimulated cAMP accumulation in isolated iris-ciliary bodies, suppression of adenylate cyclase was unlikely. It is concluded that the ocular hypotensive effect of lisuride results, in part, from activation of prejunctional dopaminergic receptors on peripheral sympathetic nerves in the anterior segment of the eye but may also involve antagonism on peripheral postjunctional α₁ adrenoceptors as well. Bilateral increases in pupil diameter antagonized by metoclopramide suggest a stimulatory action of lisuride on dopamine receptors in the central nervous system.

A new example of a morphine‐sensitive neuro‐effector junction: adrenergic transmission in the mouse vas deferens

A new example of a morphine‐sensitive neuro‐effector junction: adrenergic transmission in the mouse vas deferens

Sympathetic postganglionic cholinergic fibres

Sympathetic postganglionic cholinergic fibres

The pharmacological actions of polymethylene bistrimethylammonium salts. 1949.

The pharmacological properties of a series of polymethylene α-ωbistrimethylammonium iodides with 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, and 18 carbon atoms in the polymethylene chain have been studied. The decane derivative (C10) causes neuromuscular block in the cat in doses of 30 μg./kg. intravenously, and is the most active member of the series in this respect. During such block, the excitability of nerve and muscle is retained, the effects of acetylcholine injected arterially are paralysed, and acetylcholine release by motor nerve terminals is not prevented. Tetanization of the motor nerve or injection of acetylcholine or potassium neither diminishes nor deepens the block. A phase of potentiation of the muscle twitch, fasciculations of the muscle, and repetitive responses to single nerve volleys precedes the block. During a partial block, tetanization of the muscle leads to a well-sustained contraction. In the cat, profound neuromuscular block of the tibialis muscle may be caused by C10, without paralysis of respiratory muscles. With d-tubocurarine chloride respiratory paralysis accompanies or may precede paralysis of tibialis. C10 is 50–100 times less active by mouth than by intravenous injection. Its activity in cats anaesthetized with chloralose or pentothal is similar to that in the unanaesthetized cat; but ether appears to antagonize it slightly. Sensitivity to C10 varies greatly with species: in order of decreasing sensitivity, the series is cat-man - rabbit - monkey - mouse - rat. For d-tubocurarine chloride by the same tests, the variation in sensitivity is much smaller and decreases: rat-mouse-rabbit-cat. The action of C10 is not antagonized by anticholinesterases. The pentane and hexane homologues (C5, C6) are effective antagonists; the antagonism appears to be by competitive inhibition. Previous administration of d-tubocurarine chloride also reduces the effectiveness of C10. C10 and its neighbours elicit a contracture of the frog's rectus abdominis muscle, and do not antagonize the contracture elicited by acetylcholine. C5 and C6 do not elicit such a contracture, but antagonize the actions both of C10 and of acetylcholine. C10 can also elicit a twitch of cat's tibialis muscle if a small dose is given by close arterial injection. Members of the series, particularly C5 and C6, are able to block ganglionic transmission. Higher members possess a weak anticholinesterase action, which is more active against “true” cholinesterase than against “pseudo” cholinesterase. They also possess a weak muscarine-like action, a weak power of releasing histamine, and a feeble antibacterial action. No significant atropine-like action, or ability to stimulate autonomic ganglia, was detected. With the exception of C18, members of the series display negligible activity in depressing the surface tension of water. The pharmacological properties of the series have been related to the length of the polymethylene chain. This reveals four features: (1) a sharp maximum for potency in ganglionic block at C5–C6; (2) a sharp maximum for potency in neuromuscular block at C10; (3) a less well-defined maximum for muscarine-like activity, stimulation of frog's rectus, and anticholinesterase activity about C12; (4) a rise in antibacterial activity and surface activity beginning about C12 and still increasing at C18. The significance of the species difference, of the competitive antagonism of C5 for C10, of the variation of activity with length of polymethylene chain, and of the differences between C10 and d-tubocurarine chloride is discussed. It is a pleasure to express our indebtedness to Dr. Harold King for his interest and guidance throughout this investigation, and to our colleagues for many fruitful discussions and criticisms. We are also indebted to Dr. T. S. Work for advice on determining anticholinesterase activity, to Miss Bashford for assistance in these determinations, and to Dr. J. Niven for the histological examinations.

Role of the alpha-adrenoceptor in regulating noradrenaline overflow by nerve stimulation. 1971.

Summary . A study of the actions of phenoxybenzamine on transmitter overflow, neuronal and extraneuronal uptake of noradrenaline and in causing α‐adrenoceptor blockade was carried out using the isolated cat nictitating membrane preparation. . Phenoxybenzamine increased transmitter overflow elicited by nerve‐stimulation at 10 Hz in a concentration dependent manner in the range 10−8 to 10−5 g/ml. . Neuronal uptake of [3H]‐noradrenaline was not inhibited by concentrations lower than 10−6 g/ml of phenoxybenzamine. With 10−7 g/ml of phenoxybenzamine a significant increase in transmitter overflow was obtained, although neuronal uptake of noradrenaline was not affected. Higher concentrations of phenoxybenzamine (10−6 and 10−5 g/ml) inhibited the neuronal uptake of noradrenaline and further increased transmitter overflow. . Extraneuronal uptake of [3H]‐noradrenaline was inhibited only with the highest concentration of phenoxybenzamine tested (10−5 g/ml) and therefore appears to be unrelated to the effects on transmitter overflow. . There was a significant correlation between the degree of α‐adrenoceptor block produced by phenoxybenzamine and the increase in transmitter overflow obtained by nerve stimulation. . These results indicate that phenoxybenzamine, in addition to increasing overflow by preventing reuptake of noradrenaline, may increase transmitter release. . The possibility that phenoxybenzamine acts on α‐adrenoceptors in the adrenergic nerve terminal is discussed. These receptors would be involved in a negative feedback mechanism regulating transmitter release.

Functional morphology of the nictitating membrane in the domestic cat

Morphological differences between the corneal and palpebral surfaces of the nictitating membrane of the domestic cat were examined using histology, histochemistry and the scanning electron microscope. Both surfaces are covered by one or two layers of epithelial cells. The epithelium contains numerous goblet cells, particularly on the palpebral side. These cells revealed binding sites for six lectins as well as positive PAS reactivity, and alcianophilia at both pH 2.5 and pH 3.5. Numerous lymph follicles located on the corneal side make the epithelium look like lymphoepithelial tissue. Accumulations of lymphatic tissue may also be found on the palpebral side. Scanning electron micrographs showed microvilli on the epithelial surfaces. The function of the cat nictitating membrane is discussed on the basis of our findings and those of other authors. Movements of the nictitating membrane alternate between active and passive phases of gliding. The membrane as a whole effectively protects the nasal portion of the bulb from dust, dehydration and pathogens.

Ocular actions of an octahydrobenzo[f]quinoline: Ha117

An octahydrobenzo[f]quinoline compound, Ha117, was examined for activity on: (1) intraocular pressure and in normal, sympathectomized and water loaded rabbits and aqueous flow rate in normal and sympathectomized rabbits, respectively; (2) contractions of the cat nictitating membrane elicited by electrical stimulation of cervical sympathetic nerves; (3) cAMP accumulation in the isolated rabbit iris root-ciliary body preparation. Ha117 lowered intraocular pressure and aqueous flow rate in normal but not in sympathectomized rabbits. Elevated intraocular pressure produced by water loading was suppressed by Ha117 and pretreatment with metoclopramide antagonized the inhibitory effect of Ha117. Neuronally mediated contractions of the nictitating membrane were inhibited in a dose-related fashion by Ha117, and inhibitory effects were antagonized by domperidone. Ha117 and an analog, Ha118, did not suppress isoproterenol- and vasoactive intestinal peptide-induced accumulation of cAMP in the rabbit iris root/ciliary body. In vivo results in rabbit and cat models suggest that the ocular hypotensive effect of Ha117 is mediated by an action on prejunctional dopamine (DA 2) receptors. In vitro data in the rabbit iris root/ciliary body suggest that Ha117 and Ha118-induced lowering of intraocular pressure does not involve postjunctional suppression of cAMP accumulation.

Pharmacological evidence for heterogeneity of ocular alpha 2 adrenoceptors.

Previous studies have shown that ocular alpha 2 adrenoceptors are located prejunctionally on sympathetic neurons and postjunctionally on cells in the iris/ciliary body. While the activation of alpha 2 adrenoceptors at each site has been postulated to alter aqueous humor dynamics, little is known about the pharmacological characteristics of these receptors or their role in the modulation of anterior segment function. The purpose of the current study was to determine the possible heterogeneity of ocular alpha 2 adrenoceptors using relatively selective alpha 2 adrenoceptor agonists and antagonists to examine ocular pre- and postjunctional alpha 2 adrenoceptors. Prejunctional alpha 2 effects were evaluated by means of the cat nictitating membrane (CNM) preparation. Postjunctional alpha 2 effects were evaluated by means of the cAMP assay in rabbit iris root/ciliary body. In the CNM, the administration of UK-14, 304 (UK) produced a dose-related inhibition of neuronally mediated contractions. Pretreatment with the alpha 2 antagonist rauwolscine caused a 1 to 2 log unit right shift in the dose-response curve of UK in the CNM. However, pretreatment with alpha 2 antagonist SKF 104078 had no demonstrable effect on UK-induced inhibition of neuronally mediated contractions of the CNM. In the rabbit iris root/ciliary body, UK produced a concentration-dependent inhibition of cAMP accumulation on isoproterenol- and VIP-induced cAMP production. Pretreatment of iris root/ciliary bodies with SKF 104078 or rauwolscine reversed the inhibitory effect of UK on isoproterenol- and VIP-induced accumulation of cAMP. These data provide the first evidence that the pre- and postjunctional alpha 2 adrenoceptors represent pharmacologically distinct subpopulations of receptors in the eye.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of peripheral and central nervous system sympatholytic actions of prazosin using the cat nictitating membrane

Prazosin is a highly selective α 1-adrenoceptor antagonist that decreases blood pressure by actions on both the peripheral and central (CNS) divisions of the nervous system. The present investigation was undertaken in an attempt to characterize the relative contribution of these two sympatholytic sites of action. Submaximal contractions of the nictitating membranes were evoked by electrical stimulation of the preganglionic cervical sympathetic nerve trunk and by stimulation of the posterior hypothalamus in anesthetized cats. In initial control experiments, phenoxybenzamine (0.1–3.0 mg/kg i.v.) produced an equivalent depression of evoked nictitating membrane responses from both peripheral and CNS sites of activation which suggests only a peripheral blocking action as well as functional equivalence of the intensity of CNS and peripheral nerve stimulation. In contrast, prazosin (3–300 μg/kg i.v.) caused a differential dose-related depression of the evoked responses with ED 50s of 81.5 μg/kg (peripheral stimulation) and 12.5 μg/kg (CNS stimulation) respectively; P < 0.05. Pretreatment with rauwolscine (500 μg/kg i.v.) totally prevented the differential CNS sympatho-inhibition produced by prazosin. These results indicate that. although both CNS and peripheral sites of drug action are manifest, the ED 50 for prazosin-induced CNS sympatho-inhibition is approximately 6-fold less than that required for direct α 1-adrenoceptor blockade at the end organ. In additiom, prazosin produces CNS sympatho-inhibition indirectly by means of an α 2-adrenoceptor mechanism.

Effects of serotonin1-like receptor agonists on autonomic neurotransmission

Serotonin1A receptor agonists, 8-hydroxy-2-(di-n-propylamino)tetralin and 10-methyl-11-hydroxyaporphine, inhibited electrical stimulation-induced contraction of the guinea-pig ileum. These agonists also inhibited the pressor and tachycardiac responses to low frequency (0.25 Hz) but not to high frequency (2.0 Hz) electrical stimulation of the sympathetic nervous system in pithed rats. Serotonin1B receptor agonist RU 24969 inhibited pressor and tachycardiac responses to both low and high frequencies of stimulation in pithed rats. In the cat nictitating membrane, serotonin1A receptor agonists did not alter contractions elicited by electrical stimulation (0.1-3.0 Hz). Serotonin not only contracted the cat nictitating membrane but also facilitated contractile responses to low frequency (0.1-1.0 Hz) stimulation. The contractile effect of serotonin in the cat nictitating membrane was blunted by bretylium, methysergide, and ketanserin, but not by metoclopramide. The facilitatory effect of serotonin was antagonized by methysergide, but not by ketanserin, pindolol, propranolol, or metoclopramide. These results suggest that serotonin1A receptors modulate autonomic neurotransmission in the guinea-pig ileum and pithed rats, but not in the cat nictitating membrane. Serotonin contracts the cat nictitating mebrane via serotonin2 subtypes, while facilitating stimulated contractile responses through the serotonin1-like receptors.

Antihypertensive activity of himbacine in anesthetized cats

AbstractHimbacine is a plant alkaloid isolated from Galbulimima baccata. Intravenous administration of himbacine produced a fall in blood pressure and heart rate in anesthetized normotensive cats. These effects were similar in areflexic and normal cats, suggesting direct peripheral action with no central component involvement. Presence of himbacine did not alter the preganglionic stimulation of cat nictitating membrane, ruling out the possibility of ganglion blockade. In isolated rabbit aorta, himbacine inhibited K+‐induced contraction, an effect similar to that of papaverine. These data indicate that antihypertensive and bradycardiac actions of himbacine are mediated through its direct depressant action on myocardium and blood vessels, and that the compound is relatively safe with i.p. LD50 in mice of 230 mg/kg.

Evidence from lack of decentralization‐induced supersensitivity that β2‐ adrenoceptors of the cat nictitating membrane are non‐innervated

The right superior of cervical sympathetic trunk of cats was sectioned preganglionically under anaesthesia. Six days later the blood pressure, heart rate and contractions of the left (control) and right (decentralized) nictitating membranes were recorded under chloralose anaesthesia (80 mg kg-1). The alpha-adrenoceptor-mediated contractile responses of the nictitating membrane to intravenous adrenaline were greater on the decentralized side than the control side, with a significant shift of the dose-response curve to the left. After phentolamine (8 mg kg-1 i.v.), adrenaline administered intra-arterially exerted beta-adrenoceptor-mediated relaxation of the nictitating membranes. However, there was no difference in the sensitivity or magnitude of responses between decentralized and control sides. In a separate series of experiments, the alpha-adrenoceptor-mediated contractile responses of the nictitating membrane to intra-arterial noradrenaline displayed supersensitivity on the decentralized side, the dose-response curve being significantly shifted to the left. In the same animals, the beta-adrenoceptor-mediated relaxation responses to intra-arterial isoprenaline were non-significantly greater on the decentralized side, presumably because of raised tone. However, when expressed as a percentage of the maximum relaxation, there was no difference in sensitivity. This study shows that the alpha-adrenoceptor-mediated contractile response of the nictitating membrane displays supersensitivity after preganglionic section of the sympathetic innervation. This is presumably because of an up-regulation arising from loss of sympathetic traffic onto the receptor. The relaxation response is mediated via adrenoceptors of the beta 2-subtype and shows no supersensitivity. This suggests that these receptors are not under the influence of the sympathetic innervation.

Ocular inhibitory effects of the dopamine DA2 agonist (Ha‐118) in cats and rabbits

1. Topical administration of the dopamine (DA2) receptor agonist, Ha-118, produced unilateral ocular hypotension and miosis in normal cats. 2. The ocular hypotensive and mitotic effects of Ha-118 were not observed in surgically sympathectomized cats indicating that an intact sympathetic pathway is necessary to demonstrate activity. 3. Ha-118 caused dose-dependent suppression of contractions of the cat nictitating membrane (CNM) elicited by electrical stimulation of the pre- and postganglionic sympathetic nerve trunks but not by exogenously administered noradrenaline suggesting that Ha-118 affected prejunctional but not ganglionic or postjunctional receptors. 4. Sulpiride antagonized Ha-118-induced inhibition of neuronally mediated contractions in the CNM suggesting an interaction at DA2 receptors. 5. Topical administration of Ha-118 inhibited the rise in intraocular pressure induced by oral water loading in rabbits. 6. Topical pretreatment with metoclopramide, a DA2 antagonist, inhibited the ocular antihypertensive effect of Ha-118 in rabbits. 7. These studies demonstrate that Ha-118 decreased intraocular pressure (IOP) and pupil diameter (PD) in the cat and that this activity can be correlated with suppression of peripheral sympathetic tone in the CNM.