ISSN:8756-3320    

DOI:10.1089/jop.1985.1.1

年代:1985

数据来源: MAL

摘要:

ABSTRACTThe IOP and pupil response to α-adrenergic agonists and blockers was studied in albino rabbits. Topical ocular application of solutions of methoxamine (α1) and oxymetazoline (α2) caused dose-related early rises in IOP which were inhibited by pretreatment with prazosin, an α1-blocker, or with yohimbine, an α2-blocker. Although both prazosin and yohimbine have ocular hypotensive activity, the effect on the early IOP rise did not appear to be related to this action. Prazosin and yohimbine also inhibited the early IOP rise after treatment with clonidine, a second α2-agonist. Surgically sympathectomized rabbits showed little or no hypersensitivity to methoxamine or oxymetazoline when compared to non-operated normal rabbits. However the treated ipsilateral eyes showed a much greater increase in IOP than the treated contralateral eyes. There was little difference in the IOP response between clonidine-treated ipsilateral and contralateral eyes. Methoxamine and oxymetazoline caused dose-related increases in the pupil diameter which were blocked by the nonselective α-blocker phentolamine but not by prazosin (α1) or yohimbine (α2). This study suggests: 1) That the early IOP rise after treatment with α-agonists is due to stimulation of postsynaptic α1-receptors, possibly located in superficial blood vessels in the anterior segment of the eye; 2) The mydriatic response to α-agonists appears to be mediated by α-receptors which differ from the classical α1a

ISSN:8756-3320    

DOI:10.1089/jop.1985.1.3

年代:1985

数据来源: MAL

摘要:

ABSTRACTBecause of the need to develop ocular hypotensive agents with low incidence of side effects, the dextrorotatory enantiomers of adrenergic agents have prompted some attention. In the present study, the relative potency and efficacy of various adrenergic stereoisomers with respect to their ocular hypotensive and mydriatic effects have been determined after topical administration to conscious rabbits. The relative order of potency was found to be, iris: 1-epinephrine>>>d-epinephrine ≃ 1-norepinephrine ≃ dl-alpha-methyl-norepinephrine>dl-alpha-methyl-epinephrine>d-norepinephrine; intraocular pressure (IOP): 1-epinephrine>dl-alpha-methyl-epinephrine>d-epinephrine>dl-alpha-methyl-norepinephrine>d-norepinephrne ≃ 1-norepinephrine. The pupil and the initial ocular hypertensive responses clearly demonstrated the phenomenon of stereoselectivity of adrenergic stimulants, in that the 1-form was relatively more potent than the d-form. However, such order of potency does not seem to hold for IOP. The apparent discrepancy and reversal of order of potency for IOP responses may be related to the hypothesis that the net ocular hypotensive effect of adrenergic agents is the summation of the initial hypertension and the delayed hypotension produced by these agents. It is anticipated that the results of the present study may improve our understanding of ocular pharmacology of adrenergic stereoisomers. The ability to separate the dose-response profiles of pupillary and IOP effects of these agents may have potential therapeutic significance and thus warrants further investigation in other sp

ISSN:8756-3320    

DOI:10.1089/jop.1985.1.19

年代:1985

数据来源: MAL

摘要:

ABSTRACTTopical administration of B-HT 920 (50 μg) to the eyes of normal unanesthetized cats produced decreases in intraocular pressure and pupil diameter. The ocular hypotensive effect of B-HT 920 was eliminated by sympathectomy and pretreatment with sulpiride (2 mg/kg, s.c.). B-HT 920 also produced dose-related inhibition of contractions of the cat nictitans elicited by stimulating the pre- and postganglionic sympathetic trunks. B-HT 920-induced suppression of the contracting nictitans was antagonized more effectively by relatively selective DA2antagonists, sulpiride and domperidone, than by rauwolscine, a relatively selective α2-adrenoceptor antagonist. These data suggest that B-HT 920 produces ocular hypotension in the cat by interacting predominantly with DA2receptor on peripheral sympathetic nerve

ISSN:8756-3320    

DOI:10.1089/jop.1985.1.29

年代:1985

数据来源: MAL

摘要:

ABSTRACTSympathetic input to the anterior segment of the eyes of cats was unilaterally removed by either superior cervical ganglionectomy or treatment with 6-hydroxydopamine. Parasympathetic input was unilaterally removed by extirpation of the ciliary ganglion. Δ9-tetrahydrocannabinol ( Δ9-THC; 20 μg/hr) was delivered unilaterally to the denervated eyes and to eyes of surgically intact control catsviaosmotic minipumps and connecting extraocular cannulas over a total period of nine days. The results indicated that the degree of reduction of intraocular pressure by Δ9-THC was not affected by removal of input from either branch of the autonomic nervous system. Outflow facility during chronic administration of THC showed a two-to-three fold increase. Ciliary ganglionectomy alone produced a moderate decrease in intraocular pressure that endured for one week. These findings indicate that neither adrenergic nor cholinergic input to the cat eye is apparently required for the mediation of the tension lowering effect of THC. They additionally suggest that cholinergic input may normally play a role in the regulation of steady-state intraocular pressure levels, presumably by modulating aqueous humor format

ISSN:8756-3320    

DOI:10.1089/jop.1985.1.47

年代:1985

数据来源: MAL

摘要:

ABSTRACTThe effects of somatostatin, cyclo(D-Trp-Lys-Thr-Phe-Pro-Phe) acetate, a somatostatin analog, neurotensin, and met-enkephalin were studied in the rabbit eye by measuring the intraocular pressure (IOP), aqueous humor protein concentration, ocular blood flow and the pupil diameter. Somatostatin or the analog injected intracamerally (10 μg/eye) and infused intra-arterially (0.6-4 μg/min) had no significant effect on the parameters studied in normal eyes. However, somatostatin and, particularly, the analog attenuated the miotic response to a standard nociceptive stimulus consisting of topical application of 1% neutral formaldehyde. The other component parts of the irritative response were not attenuated. Intracameral injection of 1-2 μg neurotensin caused vasodilation in the anterior segment of the eye, a slight increase in aqueous humor protein concentration, and some decrease in IOP. Intracameral injection of 1-50 μg met-enkephalin had no effect on the blood-aqueous barrier, IOP or the pupil diameter. Neither did this dose of met-enkephalin attenuate the miotic response to exogenous substance P. It seems likely that somatostatin and the somatostatin analog attenuate the miotic response to nociceptive stimuli by preventing the release of a substance, presumably substance P, from sensory ner

ISSN:8756-3320    

DOI:10.1089/jop.1985.1.59

年代:1985

数据来源: MAL

摘要:

ABSTRACTThe toxicity of three different transdermal nitroglycerin ointments on the external ocular structures of New Zealand White rabbits was investigated. Using a randomized, double-blind protocol, both eyes of four rabbits in each of four treatment groups received 3.75 mg of either Nitrol Ointment, Nitrong Ointment, Nitro-bid Ointment, or Lacri-lube Ointment twice a day for 21 days. The eyelids, palpebral and bulbar conjunctiva, cornea, anterior chamber, and iris were evaluated by slit lamp. Pupillary size was noted and intraocular pressure was measured with an applanation tonometer. All parameters were evaluated pretreatment and two hours after the last dose on treatment days 1, 8, 15, and 22. On days 8 and 15, all four treatment groups had evidence of mild conjunctival injection; however, only the three nitroglycerin groups had mild conjunctival chemosis. At day 22, all four treatment groups had no statistically significant evidence of toxicity to the eyelid, conjunctiva, and iris. Only Nitrong Ointment produced any corneal toxicity, a mild diffuse punctate keratopathy statistically significant only on day 22. In addition, the four treatment groups showed no change in pupil size and intraocular pressure.Transdermal nitroglycerin preparations were well tolerated by the external ocular structures of rabbits. Additional animal studies to evaluate the dosage and frequency effects on tolerance and intraocular pressure are indicated.

ISSN:8756-3320    

DOI:10.1089/jop.1985.1.71

年代:1985

数据来源: MAL

摘要:

ABSTRACTSymptoms and findings arising from the systemic beta blockade caused by topical ocularly applied timolol appear shortly after drug application. We studied the systemic absorption of 20 μl of 0.5% timolol instilled unilaterally in the lower conjunctival cul-de-sac in 6 volunteers. At 3 min one subject, at 5 min three and at 8 min all but one showed measurable (≥215 pg/ml) timolol concentrations in the plasma. The rapid systemic absorption of topically applied ocular timolol observed in our study is consistent with the rapid appearance of the cardiovascular and pulmonary side effects reported in connection with timolol eye drop thera

ISSN:8756-3320    

DOI:10.1089/jop.1985.1.79

年代:1985

数据来源: MAL

摘要:

ABSTRACTA bovine eye perfusion system was developed for detoxification studies. The viability of the system was examined by two criteria: the permeability of the aqueous-blood barrier to protein, and the turnover of aqueous humor formation. Although the usefulness of the system for physiological studies is limited, the bovine eye perfusion system proved to be useful for biochemical studies of detoxification. When the system was perfused with t-butyl hydroperoxide plus the glutathione reductase inhibitor nitrofurantoin, glutathione levels of the ciliary body and iris were markedly reduced. The result was interpreted to suggest that glutathione and its redox cycling may play an important role in cellular defense against oxidative stress.

ISSN:8756-3320    

DOI:10.1089/jop.1985.1.85

年代:1985

数据来源: MAL

摘要:

ABSTRACTOpen-angle glaucoma is treated primarily with drugs, some of which have been used clinically for years. These drugs include: 1) cholinergic agonists that increase aqueous humor outflow, 2) adrenergic agonists and antagonist that affect both aqueous humor formation and outflow, and 3) carbonic anhydrase inhibitors that decrease aqueous humor formation. Several new classes of drugs are being tested for efficacy and mechanism of action. They include: 1) the D-isomer of timolol that reduces aqueous humor formation without producing adrenergic blockade, 2) dopaminergic agonists and antagonists, including bromocriptine and butyrophenones that reduce intraocular pressure, and 3) cannabinoids that reduce aqueous humor formation and increase outflow. In addition, several other types of drugs, such as prostaglandins, diuretics, Na+,K+-ATPase inhibitors, and adenyl cyclase stimulators are just now beginning to be studied.

ISSN:8756-3320    

DOI:10.1089/jop.1985.1.101

年代:1985

数据来源: MAL