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PubMed2002

Lesions of the lateral hypothalamus impair pilocarpine-induced salivation in rats.

In the present study we investigated the effects of electrolytic lesions of the lateral hypothalamus (LH) in the salivation induced by intracerebroventricular (i.c.v.) or intraperitoneal (i.p.) injection of the cholinergic agonist pilocarpine. Rats with sham or LH lesions and stainless steel cannulas implanted into the lateral ventricle (LV) were used. In rats anesthetized with urethane (1.25mg/kg of body weight) saliva was collected using pre-weighed cotton balls inserted in the animal mouth during a period of 7 min following i.c.v. or i.p. injection of pilocarpine. Injection of pilocarpine (1mg/kg of body weight) i.p. in sham-operated rats (6h, 2, 7, and 15 days after the surgery) induced salivation (497+/-24, 452+/-26, 476+/-30, and 560+/-75 mg/7 min, respectively). The effects of i.p. pilocarpine was reduced 6h, 2 and 7 days after LH lesions (162+/-37, 190+/-32, and 229+/-27 mg/7 min, respectively), not 15 days after LH lesions (416+/-89 mg/7 min). Injection of pilocarpine (120 micro g/micro l) i.c.v., in sham-operated rats (6h, 2, 7, and 15 days after the surgery) also produced salivation (473+/-20, 382+/-16, 396+/-14, and 427+/-47 mg/7 min, respectively). The salivation induced by i.c.v. pilocarpine was also reduced 6h, 2 and 7 days after LH lesions (243+/-19, 278+/-24, and 295+/-27 mg/7 min, respectively), not 15 days after LH lesions (385+/-48 mg/7 min). The present results show the participation of the LH in the salivation induced by central or peripheral injection of pilocarpine in rats, reinforcing the involvement of central mechanisms on pilocarpine-induced salivation.

Animals↗
PubMed1995

Phenylephrine and pilocarpine in the treatment of post-operative irido-corneal adhesion.

Following cataract surgery, entrapment of the iris within the surgical wound is often managed by intensive use of miotics. As the radial fibres stretch, only a small amount of fraction is exerted upon the entrapped iris. Application of a combination of phenylephrine and pilocarpine drops causes simultaneous contraction of the pupil sphincter and the radial muscle fibres. This study investigated the relative magnitude of forces induced in the iris periphery by pilocarpine and phenylephrine and the effectiveness of adding g. phenylephrine 10% to g. pilocarpine 4% drops in the treatment of postoperative irido-corneal adhesions. The investigation was divided into two parts. First, the forces induced in the iris periphery upon exposure to pilocarpine and phenylephrine were measured in 6 cadaver irises. The mean force was 27.5 +/- 5.7 x 10(-3) N for pilocarpine and 23.3 +/- 4.0 x 10(-3) N for phenylephrine. The combination of the two drugs produced a force of 54.2 +/- 6.6 x 10(-3) N (p < 0.05). In the second part of the study intensive pilocarpine 4% drops were administered to 17 patients who had iris-wound entrapment on the first post-operative day. Patients with persistent adhesion were commenced on intensive g. phenylephrine 10% and assessed after 90 minutes. Of the 17 patients, 6 responded to pilocarpine drops alone; in a further 7 the irido-corneal adhesion was released only by the addition of phenylephrine drops, and in 4 patients drops were ineffective in relieving the adhesion. This study indicates that addition of phenylephrine 10% to pilocarpine 4% drops enhances the effectiveness of pharmacological treatment of post-operative irido-corneal adhesion.

Cataract Extraction↗
PubMed1999

Pilocarpine modulates the cellular electrical properties of mammalian hearts by activating a cardiac M3 receptor and a K+ current.

1. Pilocarpine, a muscarinic acetylcholine receptor (mAChR) agonist, is widely used for treatment of xerostomia and glaucoma. It can also cause many other cellular responses by activating different subtypes of mAChRs in different tissues. However, the potential role of pilocarpine in modulating cardiac function remained unstudied. 2. We found that pilocarpine produced concentration-dependent (0.1-10 microM) decrease in sinus rhythm and action potential duration, and hyperpolarization of membrane potential in guinea-pig hearts. The effects were nearly completely reversed by 1 microM atropine or 2 nM 4DAMP methiodide (an M3-selective antagonist). 3. Patch-clamp recordings in dispersed myocytes from guinea-pig and canine atria revealed that pilocarpine induces a novel K+ current with delayed rectifying properties. The current was suppressed by low concentrations of M3-selective antagonists 4DAMP methiodide (2-10 nM), 4DAMP mustard (4-20 nM, an ackylating agent) and p-F-HHSiD (20-200 nM). Antagonists towards other subtypes (M1, M2 or M4) all failed to alter the current. 4. The affinity of pilocarpine (KD) at mAChRs derived from displacement binding of [3H]-NMS in the homogenates from dog atria was 2.2 microM (65% of the total binding) and that of 4DAMP methiodide was 2.8 nM (70% of total binding), consistent with the concentration of pilocarpine needed for the current induction and for the modulation of the cardiac electrical activity and the concentration of 4DAMP to block pilocarpine effects. 5. Our data indicate, for the first time, that pilocarpine modulates the cellular electrical properties of the hearts, likely by activating a K+ current mediated by M3 receptors.

Action Potentials↗
PubMed2001

Effect of pilocarpine 4% in combination with latanoprost 0.005% or 8-iso prostaglandin E2 0.1% on intraocular pressure in laser-induced glaucomatous monkey eyes.

PURPOSE: To compare the effect of pilocarpine, an agent that reduces uveoscleral outflow, on the ocular hypotensive efficacy of latanoprost and 8-iso prostaglandin E2 (PGE2). METHODS: Each of the two treatment groups was composed of the same eight monkeys with unilateral laser-induced glaucoma. Intraocular pressure (IOP) was measured hourly for 6 hours beginning at 9:00 AM on the baseline day (Thursday before treatment week) and on treatment days 1, 3, and 5 (Monday, Wednesday, and Friday). On all five treatment days, one drop of pilocarpine 4% was administered at 9:00 AM and 3:00 PM and one drop of latanoprost 0.005% or 25 microL of 8-iso PGE2 0.1% was administered at 10:00 AM and 4:00 PM. RESULTS: One hour after pilocarpine instillation on day 1, the reduction of IOP was similar (P > 0.90) in both treatment groups, 7.6 +/- 1.1 mm Hg (mean +/- standard error of the mean ) in the latanoprost group and 7.4 +/- 0.8 mm Hg in the 8-iso PGE2 group. However, the IOP effects of the two treatment groups became significantly different (P < 0.05) beginning 2 hours after dosing with latanoprost or 8-iso PGE, on day 1. A difference (P < 0.05) between the two groups persisted at all subsequent measurements. The reduction of IOP lessened with repeated dosing in the latanoprost and 8-iso PGE2 groups. Three hours after dosing with pilocarpine and two hours after dosing with the prostanoids, the IOP reduction was 8.3 +/- 0.9 mm Hg in the latanoprost group and 9.9 +/- 0.6 mm Hg in the 8-iso PGE2 group on day 1, and 2.1 +/- 1.0 mm Hg in the latanoprost group and 7.3 +/- 0.9 mm Hg in the 8-iso PGE1 group on day 5. CONCLUSIONS: The smaller reductions in IOP with pilocarpine and latanoprost than with pilocarpine and 8-iso PGE2 show that pilocarpine blocks much more of the ocular hypotensive effect of latanoprost than of 8-iso PGE2. The results also indicate that pilocarpine and latanoprost are mutually antagonistic. Enhancement of uveoscleral outflow appears to account for most of the ocular hypotensive effect of latanoprost and for much less of the ocular hypotensive effect of 8-iso prostaglandin E2.

Administration, Topical↗
PubMed1981

Regular fetal breathing induced by pilocarpine infusion in the near-term fetal lamb.

We report that pilocarpine, a cholinergic drug, stimulated regular sustained breathing movements in 10 near-term fetal lambs with chronically implanted catheters in the carotid artery, jugular vein, and trachea. With increasing doses of pilocarpine (0.1-5.9 mg), there was an enhanced respiratory response as measured by the duration of continuous breathing movements (14 +/- 12 min, increasing to 82 +/- 50 min; mean +/- SD), and the mean tracheal pressure per breath at end inspiration during the first 2 min after drug infusion (18 +/- 5, increasing to 38 +/- 12 mmHg). The mean pressure per breath during the control periods was 8 +/- 3 mmHg. There was no significant change in the breath frequency with increasing drug dose. A similar breathing response was not seen with epinephrine, suggesting that pilocarpine does not act by stimulating release of endogenous catecholamines. There was no fetal breathing response to pilocarpine infusion in atropine-pretreated fetal lambs, suggesting tha pilocarpine acts through a muscarinic mechanism. In eight acute experiments on exteriorized fetal lambs, we measured responses to pilocarpine before and after carotid sinus nerve ligation. The response to pilocarpine was abolished by sinus nerve section, suggesting possible mechanisms whereby pilocarpine may stimulate fetal breathing: the drug may increase peripheral chemoreceptor output, may sensitized the central respiratory centers to peripheral chemoreceptor input, of both.

Animals↗
PubMedDate not supplied

Pilocarpine hydrochloride liposomes: characterization in vitro and preliminary evaluation in vivo in rabbit eye.

Liposomes containing either pilocarpine hydrochloride or pilocarpine free base were prepared by the sonication method. This manufacturing process yielded after removal of non-encapsulated solute, small multilamellar vesicles (MLV) as was confirmed by electron microscopy examinations. For an identical liposomal composition, the encapsulation capacity and the drug content of the liposomes were drastically higher for pilocarpine hydrochloride than for pilocarpine free base. Investigation of the preparative parameters revealed that increasing the initial amount of drug decreased the drug content and the encapsulation efficiency of the liposomes formed. Since fixed amounts of lipids were used, the volume sequestration rate decrease was attributed to a moderate viscosity increase of the dispersion medium. Increase of phospholipid concentration at a constant ratio of cholesterol and dicetylphosphate to phosphatidylcholine reduced the aqueous volume entrapped per mg of lipid and subsequently the pilocarpine content in the liposomes. Negatively charged liposomes gave larger rates of pilocarpine hydrochloride and aqueous volume encapsulation than neutral liposomes but, on the contrary, positively charged liposomes gave the lowest rates of pilocarpine hydrochloride and aqueous volume encapsulation. Thus, for drug carrying the same net charge as the phospholipids an increase in the surface charge density of the liposome was not only ineffective, but actually resulted in a lower drug encapsulation due to electrostatic repulsion. Preliminary in vivo results on rabbit eyes suggested that the liposomal vehicle was probably unable to improve sufficiently the corneal penetration of pilocarpine to reach satisfactory therapeutic levels when administered at lower concentrations than commonly used.

Animals↗
PubMed2004

[Determination of three formulations of pilocarpine in rabbit ocular aqueous by RP-HPLC].

OBJECTIVE: To develop an RP-HPLC method for assay of pilocarpine in rabbit ocular aqueous humor. METHODS: The RP-HPLC method was performed on a column of ODS-C(18) with the mobile phase consisting of 0.5% of triethylamine (TEA) of phosphate solutions (10 mmol/L, pH 2.5) and acetonitrile (98/2,v/v). The detection wavelength was 215 nm and flow rate was 1.0 ml/min. Ninety albino rabbits were divided into 3 groups (30 in each):group 1 received 50 microl of eye drops containing 1% generic pilocarpine, group 21% mixture pilocarpine solution consisting of aqueous sample and liposome and group 31% liposome pilocarpine, respectively. The aqueous humor was withdrawn at 5, 10, 30, 40, 60, 90, 120, 180, 240 and 360 min. Pilocarpine was extracted from aqueous humor with dichloromethane. RESULT: The linear calibration curve was obtained in the concentration range of 0.1 - 20 microg/ml. The average recovery was (68.1+/-2.7)% (n=9). Inter-day and intra-day RSD were 4.33% and 2.87%, respectively. In three formations 1% liposome pilocarpine was the best for the areas under curve and measurable amounts. CONCLUSION: The RP-HPLC method is simple and reliable for pilocarpine measurement in ocular aqueous. Liposome formulation can significantly increase the bioavailability of pilocarpine in ocular aqueous.

Animals↗
PubMed1999

[Ocular pharmacokinetics of pilocarpine micron emulsion in rabbits].

OBJECTIVE: To compare the pharmacokinetics of pilocarpine micron emulsion with generic pilocarpine solution in the aqueous humor. METHODS: 60 albino rabbits were used and were divided into 20 groups, each consisting of 3 animals. 10 groups received 2% generic pilocarpine 50 microl as controls; 10 groups received 50 microl of 2% pilocarpine micron emulsion in the conjunctival sac. The aqueous humor was withdrawn at 5, 10, 30, 40, 60, 90, 120, 180, 240 and 360 min. after instillation. The drug was extracted from aqueous humor with dichloromethane. The drug was analyzed by reversed phase high pressure liquid chromatography (HPLC). RESULTS: Pilocarpine micron emulsion therapy gave higher aqueous humor concentration of the drug than drops at all time periods tested except 5 min. time point (P = 0.0003 - 0.042). The area under curve of micron emulsion was 3 times as much as that of drops. There was a two-fold increase in ocular bioavailability of pilocarpine due to the therapy with micron emulsion. Measurable amounts of drug following 2% micron emulsion were still observed at 360 min. while drug levels at 180 min. following 2% drop therapy were nil. CONCLUSION: Our study results demonstrated significantly increase in ocular bioavailability of pilocarpine due to the therapy with micron emulsion. Our finding indicates that a novel topical preparation of pilocarpine incorporated in micron emulsion might serve as a long acting antiglaucoma agent, and less frequent applications are necessary with it than with conventional drops.

Animals↗
PubMed2002

Oral pilocarpine: new preparation. Xerostomia after radiation therapy: moderately effective but costly.

(1) Dry mouth (xerostomia) is a frequent complication of radiation therapy for cancers of the ear nose and throat. Local measures such as saliva substitutes and anetholtrithione are either moderately effective, inadequately evaluated or little better than placebo. (2) Marketing authorization has been granted in France for an oral formulation of pilocarpine, an old parasympathomimetic agent, in the treatment of radiotherapy-induced xerostomia. (3) According to the results of two double-blind trials, pilocarpine (15-30 mg/day) improves symptoms in about 50 % of patients, compared to improvement in 25% of patients taking placebo. The drug is slow to take effect and has little impact on daily life. It is not known whether pilocarpine helps prevent the complications of xerostomia. (4) Most adverse effects of pilocarpine are due to its parasympathomimetic effects, such as sweating, urinary frequency, flushing, rhinitis and nausea. Pilocarpine must therefore be used with caution in patients with asthma, cardiac arrhythmia, iridocyclitis, and closed-angle glaucoma. (5) In France, this pilocarpine formulation costs 18 times more than a preparation of pilocarpine 2% eye drops used orally (off licence). (6) In practice, patients needing symptomatic treatment of xerostomia after radiotherapy may benefit from oral pilocarpine but, given its limited efficacy and its adverse effects, other local treatments should be tried first.

Administration, Oral↗
PubMed2003

[Temporal lobe epilepsy model induced by pilocarpine in rats].

OBJECTIVE: To characterize the acute and chronic behavioral, electrographic and histological changes of sustained seizures induced by pilocarpine in rats. METHODS: The rats in the study were divided into the experimental group and control group. After status epilepticus (SE) was induced in the experimental rats, the surviving animals were continuously monitored for 6 h-60 days. At different times after the pilocarpine injection, the animals were processed for neo-Timm and Nissl staining to visualize granule cell mossy fiber sprouting and hippocampal cell damage. RESULTS: Of the animals injected with pilocarpine, 87% developed SE, and most of the pilocarpine-induced SE rats (20%-100%) showed recurrent seizures during the chronic period. A widespread cell loss was noted in the hippocampal formation of the rats with pilocarpine-induced SE. The pattern of neo-Timm staining in the inner molecular layer was clearly altered in animals that showed pilocarpine-induced SE. The Neo-Timm staining score of the experimental group was significantly higher than that of the control group. The degree of inner molecular layer mossy fiber terminal staining increased with time after the epileptogenic lesion. CONCLUSION: The temporal lobe epilepsy model induced by pilocarpine in rats can replicate several of the features of human temporal epilepsy (hippocampal cell loss, inner molecular layer mossy fiber sprouting, and spontaneous recurrent seizures), and it may be a useful model for studying this human temporal lobe epilepsy. The results also suggest that structural brain damage insulted by pilocarpine-induced SE may underlie or be associated with recurrent spontaneous seizures in rats.

Animals↗
PubMed1987

Treatment of elevated intraocular pressure with concurrent levobunolol and pilocarpine.

Between July 1983 and January 1986, 54 patients with open-angle glaucoma or ocular hypertension were treated for 3 months with 2% pilocarpine hydrochloride (given four times daily) and one of two beta-adrenoceptor blocking drugs, levobunolol hydrochloride (0.5% [17 patients] or 1% [19 patients]) or 0.5% timolol maleate (18 patients), given twice daily. Before entry into the study all patients had had stable intraocular pressure (IOP) with treatment with 0.5% timolol and 2% pilocarpine. Stable IOP was successfully maintained in up to 88% of the patients in the two levobunolol-pilocarpine groups and in 83% of those in the timolol-pilocarpine group. Two patients experienced adverse reactions: one, who received timolol and pilocarpine, suffered blepharoconjunctivitis, and the other, who received 1% levobunolol and pilocarpine, experienced bradycardia. The results indicate that the levobunolol-pilocarpine regimens were as safe and effective as the timolol-pilocarpine regimen in stabilizing IOP.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

The seizures induced by pilocarpine: behavioral, electroencephalographic and neuropathological studies in rodents.

Seizures produced by systemic administration of pilocarpine hydrochloride, a cholinergic muscarinic agonist, in rodents are proposed as a useful animal model of epilepsy. Pilocarpine-induced seizures in rats and mice are characterized by sequential development of behavioral and electrographic signs, which are followed by widespread damage to the forebrain (hippocampus, amygdala, thalamus, olfactory cortex, neocortex and substantia nigra). Spontaneous seizures may be observed in the long-term period following the administration of convulsant doses of pilocarpine. In experiments designed to examine neuronal networks engaged in the generation and spread of pilocarpine-induced convulsions, a marked role for the basal ganglia is demonstrated. The caudate-putamen, the substantia nigra and the entopeduncular nucleus were found to govern the propagation of seizures produced by pilocarpine. The antiepileptic potential of drugs (diazepam, clonazepam, phenobarbital, valproic acid and trimethadione) against pilocarpine-induced convulsions correlates with their depressant action on the spontaneous activity of non-dopaminergic cells in the substantia nigra. Developmental studies show age-dependent differences in the convulsant response of rats to pilocarpine and status epilepticus are first noted in 2-3 week-old rats, but there is no clear-cut correlation between seizures and evolution of brain damage at this age. The adult pattern of the damage to forebrain is seen after a delay of 1-2 weeks relative to the development of seizures and status epilepticus. The research on the pilocarpine model of convulsions and other cholinergically mediated seizure syndromes may be of value for designing new therapeutic approaches to epilepsy in.

Animals↗
PubMed1983

[Effect on pressure after instillation of a drop of depot-pilocarpine. Clinical results of its medium-term action].

A clinical comparison of an emulsion containing a new pilocarpine polymer (Polym) compound to that of a traditional pilocarpine salt solution (Plc) on the intraocular pressure (IOP) has been performed in 40 open-angle patients treated with the long acting pilocarpine-complex for 120 days. The treatment protocol was divided into 3 stages: Stage 1 is a single dose treatment where 12 patients were divided randomly into 2 groups of 6 each. The patients of each group were given 1 drop into each eye: 1 drop every 12 hours for Polym, 1 drop every 6 hours for Plc. The patients were observed for a period of 24 hours. After 24 hours without medication, the treatments were crossed over and nycthemeral graph curves were registered for both groups. Stage 2 is a medium term study were the 12 patients used in Stage 1 were added to another 28 patients. All 40 were then assigned to 1 of 2 treatment groups (2 groups of 20 patients each) according to a table of random numbers. Treatments were administered during one month, then cross-overed again during 4 weeks. Stage 3: finally, every patient could choose his treatment (either Polym or Plc) for the rest of the period (2 months). The clinical study shows that the polymer complex (Polym) produced a prolonged therapeutic effect, this being consistant with a slow release pattern and maintained a more effective around-the-clock control than pilocarpine solution. These results were accomplished by two applications per day as compared to the four necessary applications of Plc, on a half daily pilocarpine dose with Polym. The medium term results confirmed the efficacity noted in the short term survey. Most patients preferred Polym to Plc when they were asked. Throughout the 4 months study period, no adverse side effects were reported. Visual disturbances characteristic of pilocarpine eye-drops were reduced from 3 times a day on pilocarpine salt solution to once a day on pilocarpine polymer complex.

Adult↗
PubMed1984

Alteration of acetylcholine synthesis by pilocarpine. In vivo and in vitro studies.

Imidazole activates synthesis of acetylcholine by choline acetyltransferase. Pilocarpine hydrochloride, an imidazole derivative, was investigated for its activation effect. In vitro, millimolar concentrations of pilocarpine significantly activated human ciliary body and retinal and rabbit corneal epithelial, iris-ciliary body, and retinal choline acetyltransferases. Concentrations greater than 100mM pilocarpine inhibited acetylcholine synthesis. In vivo, 1% or 4% pilocarpine eyedrops given every 30 minutes for four applications failed to significantly alter rabbit ocular acetylcholine levels. There was a tendency for pilocarpine-treated eyes to have lower levels of acetylcholine. Although pilocarpine altered acetylcholine synthesis by human and rabbit ocular tissues in vitro, this phenomenon could not be demonstrated in rabbits in vivo. However, because tissues of intact rabbit eyes degrade pilocarpine, the possibility remains that this drug can alter acetylcholine synthesis when applied to the intact human eye.

Acetylcholine↗
PubMed1992

Timolol-pilocarpine fixed-ratio combinations in the treatment of chronic open angle glaucoma. A controlled multicenter study of 48 weeks. Scandinavian Timpilo Study Group.

The effect of the fixed combination of 0.5% timolol maleate with 2% pilocarpine hydrochloride given twice a day and 0.5% timolol with 4% pilocarpine given twice a day was tested in a long-term, multicenter study. A total of 360 patients with open angle glaucoma were included; they were defined as those who had intraocular pressure greater than 21 mm Hg while receiving single, topical antiglaucoma therapy. Primarily, the purpose of the study was to investigate the efficacy of 0.5% timolol-2% pilocarpine, and second, to see to what extent an increase in concentration to 0.5% timolol-4% pilocarpine would further lower intraocular pressure in those patients with an intraocular pressure of greater than 21 mm Hg while taking 0.5% timolol-2% pilocarpine. The cohort of 228 patients went through the examinations for a total of 48 weeks. A mean decrease in intraocular pressure from 24.7 +/- 2.8 to 21.0 +/- 3.8 mm Hg was observed. During the trial, approximately 33% of the patients required an increase in concentration to 0.5% timolol-4% pilocarpine after the week 8 examination. At week 12, in those using 0.5% timolol-4% pilocarpine, an additional 2.2 mm Hg lowering of intraocular pressure was observed. Side effects were minor and temporary and did not necessitate withdrawal from the study.

Adult↗
PubMed1977

Quantitative analysis of degradation products in pilocarpine hydrochloride ophthalmic formulations.

The presence of isopilocarpine, an epimer of pilocarpine, and of pilocarpinic acid, a hydrolytic degradation product of pilocarpine, was established and all three substances were assayed in various commercial ophthalmic formulations of pilocarpine hydrochloride by 13C-Fourier transform spectroscopy. Assay was based upon integrated intensities of selected resonances from any formulation calibrated against the intensity of tetramethylammonium bromide, used as a common external reference. The normalized intensities were then related to those of a reference solution of pilocarpine hydrochloride, thereby eliminating any factor arising from variability of 13C-relaxation times. The 13C-resonance for the N-methyl group, being common to all products, provides a convenient basis for the assay of the total alkaloid content whereas the C-8 resonances are best suited for assaying residual pilocarpine and its degradation products. This procedure, estimated as accurate to +/- 5%, constitutes the first comprehensive analytical method to differentiate between pilocarpine and its degradation products.

Carbon Isotopes↗
PubMed2000

Low doses of pilocarpine do not significantly increase outflow facility in the cynomolgus monkey.

Low doses (10(-9)-10(-6) M) of pilocarpine reportedly increase outflow facility in the organ-cultured human eye, suggesting a direct action on the trabecular meshwork. M3 muscarinic receptors have been found in both cultured human trabecular meshwork cells and tissue. We determined whether low pilo doses would increase outflow facility in the living monkey. The anterior chambers of both eyes of 17 pentobarbital anesthetized cynomolgus monkeys were cannulated and outflow facility measured bilaterally by 2-level constant pressure perfusion after an initial 2 ml exchange with Bárány's perfusand containing 24.5 microM phenylephrine (PE). Two subsequent exchanges were performed with one eye receiving Bárány's + PE + 10(-10)-10(-4) M pilocarpine and the contralateral eye receiving only Bárány's + PE. Outflow facility was measured for 35-40 min following each exchange. Accommodation and pupil diameter were measured before each exchange and approximately every 10 min during facility measurements. Outflow facility was significantly increased by 154 and 313% in eyes treated with 10(-5) M and 10(-4) M pilocarpine, respectively, related to contralateral controls. Accommodation and miosis also were induced only at 10(-5) M (accommodation, 3.3 +/- 1.6 diopters, NS; miosis, -4.1 +/- 0.5 mm, P < or = 0.001) and 10(-4) M (accommodation, 10.6 +/- 0.0 diopters, P < or = 0.02; miosis, -3.4 +/- 1.0 mm, P < or = 0.025) pilocarpine. We conclude that low anterior chamber doses of pilocarpine do not increase outflow facility in the living monkey as reported in the organ-cultured human eye, nor do they induce miosis or accommodation. All three parameters respond to pilocarpine at similar doses, and there is no functional evidence of a meaningful outflow facility-relevant pilocarpine effect on the trabecular meshwork at doses lower than those which affect the ciliary muscle.

Accommodation, Ocular↗
PubMed1989

Assessment of the muscarinic receptor subtype involved in the mediation of pilocarpine-induced purposeless chewing behaviour.

Purposeless chewing behaviour in rats was enhanced by intraperitoneal administration of the muscarinic agonists pilocarpine (1.0-8.0 mg/kg), RS 86 (0.5-0.8 mg/kg), oxotremorine (1-2 mg/kg) and arecoline (2-32 mg/kg), but not by nicotine (0.1-3.2 mg/kg). Chewing behaviour was also induced by the ICV administration of the muscarinic agonists carbachol (12.5-100 micrograms) and pilocarpine (50-200 micrograms), but not by the putative M-1 receptor agonist McN-A-343 (50-200 micrograms) or AH 6405 (100-200 micrograms). The muscarinic receptor antagonists scopolamine (0.01-0.1 mg/kg SC), benzhexol (0.075-2.5 mg/kg SC), secoverine (1-10 mg/kg SC), and dicyclomine (1.25-10 mg/kg SC) antagonised purposeless chewing behaviour induced by pilocarpine (4 mg/kg IP). AF-DX 116 (2.5-100 mg/kg SC), an M-2 antagonist, partially inhibited the actions of pilocarpine (4 mg/kg IP). Based on ED40 values the rank order of potency following IP administration was scopolamine greater than benzhexol greater than secoverine greater than dicyclomine greater than AF-DX 116. The ICV administration of the muscarinic antagonists N-methylscopolamine (2.5-10 micrograms) and oxyphenonium (10-40 micrograms) antagonised chewing behaviour induced by pilocarpine (4 mg/kg IP) in a dose-related manner. The M-2 antagonist 4-DAMP (40-160 micrograms ICV), as well as AF-DX 116 (40-160 micrograms ICV), also inhibited the effects of pilocarpine (40-160 micrograms ICV). The putative M-1 receptor antagonist pirenzepine (80-320 micrograms ICV) did not antagonise chewing behaviour induced by pilocarpine (4 mg/kg IP).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗