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Biomedical subjects

D E Potter

Publications and source records attributed to D E Potter.

At least 55 records · Page 3Linked to original sources
PubMed1991

Medetomidine-induced alterations of intraocular pressure and contraction of the nictitating membrane.

The alpha-2 adrenoceptor agonist, medotomidine (MED), was examined for effects on: (1) intraocular pressure (IOP) in normal and sympathectomized (SX) rabbits; (2) IOP in normal rabbits pretreated with the alpha-2 antagonist idazoxan; (3) contractions of the cat nictitating membrane (CNM) elicited by nerve stimulation and intra-arterial (IA) norepinephrine. Unilateral topical administration of MED (7.5-75 micrograms) caused dose-dependent, bilateral IOP reduction in normal eyes, but MED (25 micrograms) had no appreciable hypotensive activity in SX eyes. The ocular hypotensive effect of MED (25 micrograms) was antagonized by treatment with idazoxan (100 micrograms, bilaterally), a relatively selective alpha-2 antagonist. MED and dexmedetomidine (DMED) also inhibited frequency-related contractions of CNM induced by electrical stimulation of the cervical sympathetic trunk. Rauwolscine (100 micrograms, IA) shifted the MED dose response in the CNM to the right indicative competitive antagonism, whereas SK&F 104078 (300 micrograms, IA), a relatively dose-selective postjunctional alpha-2 antagonist, had no effect on DMED suppression. These results show that MED lowers IOP in part, by interacting with alpha-2 adrenoceptors located on sympathetic nerve endings. An effect of MED on imidazoline sites may also be possible.

Administration, Topical↗
PubMed1990

Prejunctional adrenoceptor activity of N-0437: a relatively selective DA2 dopamine receptor agonist.

Prejunctional adrenoceptor activity of N-0437, 2[N-n-propyl-N-2-(thienylethyl-amino)-5-hydroxytetralin], was investigated by means of the cat nictitating membrane (CNM) preparation. Intra-arterial (i.a.) administration of N-0437 produced a dose-related inhibition (ED50 = 14 micrograms) of the CNM contractions elicited by electrical stimulation of pre- and postganglionic sympathetic nerves of the superior cervical ganglion. Pretreatment with domperidone i.a., a relatively selective DA2 receptor antagonist, markedly attenuated the CNM response to racemic N-0437 (ED50 = 6.7 x 10(2) micrograms). However, pretreatment with rauwolscine i.a., a relatively selective alpha 2-receptor antagonist, did not alter the CNM responses to racemic N-0437. Evaluation of the (R)-(+) and (S)-(-) enantiomers showed that only the (S)-(-) enantiomer was active in suppressing the contractions in the CNM preparation. These results demonstrate that N-0437 is a potent agonist for prejunctional DA2 dopamine receptors on peripheral sympathetic nerves in the CNM and that these peripheral DA2 receptors appear to be enantioselective.

Animals↗
PubMed1990

Review: alpha 2 and DA2 agonists as antiglaucoma agents: comparative pharmacology and clinical potential.

Alpha-2 (alpha 2) and DA2 agonists lower intraocular pressure (IOP) in laboratory animals and man. Like beta-blockers, alpha 2 and DA2 agonists appear to lower IOP by reducing aqueous inflow. These agents share a common mode of action on sympathetic nerve terminals, where they modulate the release of neurotransmitters. However, one can demonstrate that peripheral prejunctional alpha 2 and DA2 receptors on sympathetic neurons are separate entities by utilizing selective agonists and antagonists. In addition to their prejunctional actions, alpha 2 agonists act postjunctionally in the iris root/ciliary body (IRCB). Moreover, utilizing selective postjunctional alpha 2 adrenoceptor antagonists, heterogeneity can be demonstrated between ocular pre- and postjunctional adrenoceptors. Stimulation of postjunctional alpha 2 adrenoceptors in the IRCB can inhibit the cellular responses to endogenous neurotransmitters and hormones that are coupled positively to adenylate cyclase. Based upon these observations, one can predict that alpha 2 agonists should have a broader spectrum of action in the eye than beta-receptor antagonists. Three bioassays were used in the activity analysis of alpha 2 and DA2 agonists. Prejunctional (neuronal) activity was determined in the cat nictitating membrane preparation in which frequency-related (2-8 Hz), neuronally induced contractions were inhibited by these compounds. Postjunctional activity was assayed on isolated rabbit IRCB tissue where cAMP levels were stimulated by either isoproterenol or VIP in the absence and presence of the test agonist (alpha 2 or DA2). In this system, it has been demonstrated that alpha 2 agonists have inhibitory properties, but DA2 agonists are inactive.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗
PubMed1990

Effect of the calcium antagonist, nifedipine, on ischemic retinal dysfunction.

The therapeutic effectiveness of calcium channel antagonists (CCA) in hypertension and angina are well established. More recently, CCAs have also been demonstrated to ameliorate neurologic dysfunction that often accompanies ischemia associated with subarachnoid hemorrhage and stroke. We have hypothesized that retinal degeneration associated with ischemia may also result from the accumulation of calcium intracellularly, so-called "Ca++ overload". To test this hypothesis, a rat model of acute retinal ischemia, produced by direct occlusion of posterior ciliary and central retinal arteries, was developed. The extent of retinal dysfunction induced by ischemia was evaluated by electroretinograms (ERGs). Occlusion of the retinal arteries resulted in the disappearance of both a- and b-waves during the occlusion period (30 minutes) in vehicle-treated rats. Total retinal ischemia did not produce any significant change in magnitude of ERG a-wave amplitude during three-hours of reperfusion. However, ERG b-waves amplitudes were significantly reduced by more than 60%. In rats, pretreatment with nifedipine (0.33 to 3.3 mg/kg, i.p.) 30 minutes prior to the occlusion of the retinal vessels produced a significant dose-dependent increase in the recovery of b-wave amplitude when compared to vehicle-treated rats. These data support the idea that "Ca++ overload", resulting from the deregulation of intracellular Ca++ homeostasis, is a primary factor involved in ischemic retinal degeneration and that CCAs can protect the retina from ischemic damage.

Animals↗
PubMed1990

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.

Animals↗
PubMed1988

LY141865: a relatively selective DA2 agonist with complex ocular activity.

LY141865 (LY), an ergoline derivative, was investigated for ocular effects in rabbits and monkeys. LY lowered intraocular pressure (IOP) bilaterally in monkeys and rabbits, prevented the bilateral rise in IOP caused by oral waterloading in rabbits and slowed the rate of IOP recovery bilaterally in rabbits. The ocular hypotensive activity of LY in rabbits was inhibited by sympathectomy and pretreatment with sulpiride. Since LY has cardiovascular effects that are centrally mediated, ocular responses may also be mediated, in part, by an action in the CNS.

Animals↗
PubMed1988

Ocular and cardiac beta-antagonism by timolol prodrugs, timolol and levobunolol.

Topically applied O-butyryl timolol, O-pivaloyl timolol and levobunolol (0.25 micrograms) antagonized isoproterenol-induced ocular hypotension for 8 hrs whereas timolol (0.25 micrograms) was shorter acting (4 hrs). Timolol (25 micrograms) produced greater antagonism of isoproterenol-induced tachycardia than did O-butyryl and O-pivaloyl timolol (25 micrograms). These results suggest that, at similar doses, O-butyryl and O-pivaloyl timolol produce high concentrations of timolol in ocular tissues and undergo redistribution more slowly into the systemic circulation than does topical timolol. Under certain circumstances, prodrugs may provide a mechanism for increasing selectivity and extending the duration of action in the target organ as well as decreasing systemic effects.

Adrenergic beta-Antagonists↗
PubMed1987

Dihydrolevobunolol is a potent ocular beta-adrenoceptor antagonist.

The ocular beta-adrenoceptor antagonist activity of dihydrolevobunolol (DHLB), the major ocular and systemic metabolite of levobunolol was investigated by determining its ability to block isoproterenol-induced ocular hypotension in normotensive rabbits. Topically-applied 0.001% and 0.01% DHLB virtually abolished the response to isoproterenol, indicating a beta-blocking potency similar to that of timolol. Thus, the ocular metabolism of levobunolol leads to the formation of a highly potent beta-adrenoceptor antagonist that may contribute to its clinical efficacy.

Adrenergic beta-Antagonists↗
PubMed1987

Cianergoline lowers intraocular pressure in rabbits and monkeys and inhibits contraction of the cat nictitans by suppressing sympathetic neuronal function.

Dopamine (DA1 and DA2) receptors have been demonstrated functionally in the anterior segment of the eye. Previous results have indicated that bromocriptine, a relatively selective DA2 agonist, can lower intraocular pressure (IOP) in laboratory animals as well as in normal and glaucomatous humans. Other ergoline derivatives (pergolide, lergotrile, LY141865) have also been demonstrated to lower IOP in laboratory animals. Cianergoline, a new ergoline derivative, was tested for: 1) ocular hypotensive activity in normal and sympathectomized (SX) rabbits and in normal capuchin monkeys, 2) inhibition of induced ocular hypertension by waterloading in rabbits and 3) suppression of contractions of the cat nictitating membrane (CNM) elicited by electrical stimulation of sympathetic nerves and by intraarterial (i.a.) injection of norepinephrine (NE). Topically administered cianergoline (0.022-0.22 mg) produced dose-related, unilateral ocular hypotension in normal but not in SX rabbits. In addition, cianergoline (0.5 mg) produced a slight reduction of IOP in capuchin monkeys. There were no significant effects on iris function in rabbits, however, miosis did occur in the monkeys. Cianergoline (0.22mg) suppressed ocular hypertension induced by waterloading in rabbits, and this effect was antagonized by metoclopramide, a relatively selective DA2 antagonist. Cianergoline (1-333 micrograms, i.a.) also produced dose-related inhibition of neuronally mediated contractions of the CNM. Cianergoline inhibited low frequency (2 & 4 Hz) contractile responses of the CNM more than high frequency (6 & 8 Hz) responses. Contractions of the CNM caused by i.a. NE were also inhibited by higher concentrations of cianergoline. These data demonstrate that cianergoline, like bromocriptine, can lower IOP and that the predominant mechanism involves inhibition of sympathetic neuronal function at prejunctional (DA2) and postjunctional (alpha 1) adrenoceptors.

Animals↗
PubMed1987

Ocular effects of a N,N-disubstituted 5-OH aminotetralin (N-0437): evidence for a dual mechanism of action.

The selective DA2 agonist, N-0437, produced an acute reduction in intraocular pressure (IOP) and pupil diameter (PD) when applied topically to the eyes of normal monkeys. Ocular hypotension and miosis were primarily unilateral in nature, dose-related and lasted 3 to 5 hours following drug instillation. In normal monkeys, 24 to 48 hours following drug administration, a secondary chronic (greater than 24 hrs) reduction in pressure was observed. Once-a-day topical administration of N-0437 (250 micrograms), to normal monkeys, for 4 days produced a chronic unilateral reduction in IOP that persisted for 18 days. Associated with this reduction in pressure on day 2 through 6 were miosis and ptosis of the treated eye. Although topical administration did not lower IOP in rabbits, intracameral injection of N-0437 significantly depressed IOP for 3 days when compared to control injected eyes. Evaluation of ocular sympathetic innervation in N-0437 treated rabbits indicated that these fibers were not functional. In rabbits, intracameral administration of the active (S,-) and inactive (R,+) enantiomer of N-0437 produced equivalent reductions in pressure. These data provide further support for the hypothesis that DA2 receptor agonists can produce acute reductions in IOP. In addition, N-0437 appears to have a second non-receptor mediated mechanism of action that produces a chronic reduction in IOP. This chronic reduction in pressure appears, in part, to result from an interruption of ocular sympathetic nerves function.

Administration, Topical↗
PubMed1987

Aporphine derivatives affect ocular function in diverse ways.

The sympathetic nervous system has been implicated in the ocular effects of several classes of dopamine receptor agonists. Two agonists of the aporphine class, (-) N-propylnorapomorphine [-)NPA) and norapomorphine (NA), were evaluated for effects on intraocular pressure (IOP) and pupil diameter (PD) in cats and normal (NL) and sympathectomized (SX) rabbits and on contractions of the cat nictitating membrane (CNM). Topically administered (-)NPA produced a monophasic IOP drop in the ipsilateral eye and a biphasic (increase, decrease) IOP response in the contralateral eye of normal rabbits. Pupil diameter increased bilaterally. In NL cats, the ipsilateral IOP and PD response to (-)NPA was biphasic (increase, decrease) and the contralateral IOP response was monophasic (increase). (-)NPA produced an increase in spontaneous motor activity (SMA) in rabbits and cats. NA lowered IOP unilaterally in NL rabbits. In SX rabbit eyes, (-)NPA lowered IOP as much as in NL eyes but with less mydriasis. NA did not lower IOP in SX rabbit eyes. Both (-)NPA and NA inhibited contractions of the CNM elicited by electrical stimulation of the pre- and post-superior cervical ganglionic nerves. (-)NPA, but not NA, inhibited contractions elicited by exogenous norepinephrine. These results suggest that aporphine derivatives produced two diametrically opposed effects on ocular function; 1) a centrally mediated effect that enhanced noradrenergic activity to elicit mydriasis, SMA and ocular hypertension, and 2) a peripherally mediated effect to produce miosis and ocular hypotension.

Animals↗
PubMed1986

Effects of ibuterol, a beta-2 adrenergic prodrug, on intraocular pressure.

Ibuterol, a prodrug of terbutaline, was approximately 100 times more potent than terbutaline in producing ocular hypotension in the treated eye of normal and sympathectomized (SX) rabbits. In normal rabbits, ibuterol produced no change in IOP of the contralateral eye whereas in unilaterally SX rabbits a rise in IOP occurred in the SX (contralateral) eye when the normal eye was treated with ibuterol. Ibuterol also suppressed ocular hypertension induced by water loading and delayed the IOP recovery rate although its onset of action was delayed. Aqueous flow was increased significantly at 1 hr after ibuterol in fluorophotometric studies in normal rabbits. Pretreatment with forskolin antagonized rather than enhanced ibuterol-induced ocular hypotension. Pretreatment with diclofenac failed to suppress the development of tachyphylaxis to the ocular hypotensive effect of ibuterol. Although ibuterol is an effective ocular hypotensive agent in rabbits, the effects of this agent on aqueous flow are complex and tachyphylaxis to the ocular hypotensive effect develops fairly rapidly.

Animals↗
PubMed1986

The ocular effects of xylazine in rabbits, cats, and monkeys.

Xylazine is an agent frequently used in combination with ketamine to anesthetize rabbits. Xylazine is also related pharmacologically to clonidine, a relatively selective alpha 2-agonist. In the present studies, xylazine was examined for its effects on intraocular pressure (IOP) and pupil diameter (PD) in rabbits, cats and monkeys and on noradrenergic function in the cat nictitating membrane (CNM) preparation. Topical and unilateral administration of xylazine (1.0 mg) lowered IOP bilaterally in normal, unanesthetized rabbits, cats and monkeys and caused unilateral miosis in rabbits and cats. These ocular effects of xylazine were attenuated in superior cervical ganglionectomized (SX) cats and rabbits. In addition, intra-arterially administered xylazine (10, 33 and 100 micrograms) produced dose-related inhibition of contractions of the CNM elicited by electrically stimulating the pre- and postganglionic sympathetic trunks without altering the response to i.a. norepinephrine (10 micrograms). These data suggest that ocular effects of xylazine are mediated, in part, by alteration of sympathetic neuron function. Xylazine suppressed ocular hypertension induced by water loading and IOP recovery rate following hypertonic saline infusion in rabbits suggesting that aqueous flow was inhibited. Topical pretreatment with 0.05 mg of timolol caused potentiation of the ocular hypotensive response to 0.05 mg of xylazine in rabbits. These results indicate that xylazine lowers IOP, in part, by suppressing sympathetic neuronal function which causes a reduction in aqueous flow. The augmented response to timolol and xylazine, as compared with either agent alone, suggests a rational basis for combining a prejunctionally active agent with a postjunctionally active one.

Animals↗
PubMed1986

Ocular effects of a relatively selective alpha 2 agonist (UK-14, 304-18) in cats, rabbits and monkeys.

UK-14, 304-18 (UK), a relatively selective alpha 2-agonist, was examined for its effects on intraocular pressure (IOP) and pupil diameter (PD) in rabbits, cats and monkeys and on noradrenergic function in the cat nictitating membrane (CNM) preparation. Topical, unilateral administration of UK (0.0005-0.5 mg) produced dose-dependent decreases in IOP and pupil size in normal, unanesthetized rabbits, cats and monkeys. The ocular hypotensive effect of UK in the ipsilateral eye was delayed relative to the contralateral eye in all three species; UK produced an initial transient ocular hypertension in rabbits which was abolished by surgical transection of three major extraocular muscles. Mean arterial blood pressure in rabbits was not affected by 0.005 mg UK topically. The ocular hypotensive and miotic effects of UK were attenuated in superior cervical ganglionectomized (SX) cats and rabbits. Intra-arterially administered UK (0.33, 1.0, 3.3 and 10 micrograms) produced dose-related systemic hypotension and inhibition of contractions of the CNM elicited by electrically stimulating the pre- and postganglionic sympathetic trunks in the urethane/chloralose anesthetized cat. This inhibition was reversed and prevented by 300 micrograms rauwolscine but not by 300 micrograms domperidone. UK also enhanced the contractile response of the CNM to injected norepinephrine (10 micrograms). UK suppressed ocular hypertension induced by water loading and IOP recovery rate following hypertonic saline infusion in rabbits suggesting that aqueous flow was inhibited. These results indicate that UK lowers IOP, in part, by suppressing sympathetic neuronal function which causes a reduction in aqueous flow.

Adrenergic alpha-Agonists↗
PubMed1986

Comparison of continuous ambulatory peritoneal dialysis and hemodialysis in children.

The clinical course of 51 children, 0.2 to 20 years, treated with CAPD, and 25 children, 3 to 18 years, treated with chronic hemodialysis was compared over a 5 1/2 year period. The CAPD patients had higher hematocrit levels, higher serum carbon dioxide and cholesterol levels, lower BUN and serum albumin levels, and lower blood pressure levels than the hemodialysis patients. Linear growth was better in the CAPD patients with one method of assessment, but not with another. Complications were more frequent in the CAPD patients; the peritonitis rate was one episode per 7.2 patient-months and there were 46 failures of peritoneal catheters compared with 12 failures of hemodialysis access. Five CAPD patients died and seven transferred to hemodialysis, whereas one hemodialysis patient died and four transferred to CAPD. Although some advantages of CAPD were demonstrated in this study, the high complication rate and unexpectedly high mortality rate observed with CAPD were disturbing and indicate the need for further evaluation of this form of therapy.

Child↗
PubMed1985

Mechanism of the ocular hypotensive action of ketanserin.

Ketanserin has been characterized as a relatively selective antagonist for serotonin (5-HT2) receptors. However, recent evidence suggests that ketanserin can also antagonize activity at alpha 1-adrenoceptors. Topically applied ketanserin lowered intraocular pressure (IOP) in rabbits, cats, and monkeys. Ketanserin also suppressed ocular hypertension induced by waterloading and the IOP recovery rate in response to hypertonic saline. In contrast, the ocular hypotensive activity of ketanserin was markedly attenuated in sympathectomized (SX) rabbits. In the cat nictitating membrane, ketanserin produced dose-related inhibition of contractions elicited by neuronal stimulation and by intra-arterial injection of norepinephrine. These data demonstrate that ketanserin: 1) lowers IOP more effectively in eyes with intact sympathetic innervation than in SX eyes, 2) appears to lower IOP by suppressing aqueous inflow, and 3) acts primarily by antagonizing the action of norepinephrine on alpha 1-adrenoceptors.

Animals↗