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At least 19 recordsLinked to original sources
PubMed1977

Pilocarpine-induced subsensitivity to carbachol and pilocarpine of ciliary muscle in vervet and cynomolgus monkeys.

Vervet monkeys were given unilateral treatment for two weeks with one 2% pilocarpine eye drop three times daily between 8 a.m. and 6 p.m. (night interval 14h) and were then subjected to anterior chamber perfusion 20 mug pilocarpine intracamerally caused similar and substantial increases in outflow facility in both eyes. Cynomolgus monkeys were unilaterally treated with continuous release of 33 mug/h of pilocarpine for 5-6 days. The facility response to 1 mg/kg pilocarpine iv was small or absent on the treated side. Iridectomized cynomolgus monkeys responded with 12.6+/-5.2 (SD) diopters accommodation to 1.5 mg/kg pilocarpine im, with very similar responses in the two eyes. During continuous release of 30 mug/h pilocarpine, accommodation of the treated eye dropped grdually and after 4-8 days treatment the accommodative response was markedly reduced to pilocarpine 1.5 mg/kg im or 100 mug topically. The degree of subsensitivity was much less when tested with either systemic or topical carbachol. This was also the case in a few vervet experiments. Recovery of full pilocarpine sensitivity took several weeks in the cynomolgus monkey. As an explanation for the excessive subsensitivity and large interindividual differences found with pilocarpine, an individually variable, nonmuscarinic relaxant action counteracting the muscarinic excitatory action is suggested. Clinical implications of this hypothesis are discussed.

Accommodation, Ocular↗
PubMed1993

Inhibitory effect of pilocarpine on norepinephrine release from electrically stimulated iris dilator muscles of rabbits as a most possible mechanism of pilocarpine-induced miosis.

Instillation of pilocarpine-induced a miosis in a rabbit. In an isolated iris sphincter muscle of rabbit, pilocarpine induced a small contraction and behaved as an antagonist of carbachol. The contractile response of an isolated rabbit dilator muscle to a field stimulation was inhibited by pilocarpine. This inhibitory action of pilocarpine was antagonized by atropine in a concentration-dependent manner. An amount of norepinephrine released from the electrically stimulated dilator muscle was inhibited by pilocarpine. The inhibitory effect of pilocarpine on norepinephrine release was decreased by atropine. A following explanation is proposed as a most possible mechanism for the pilocarpine-induced miosis in the rabbit. Pilocarpine activates the prejunctional cholinoceptors to inhibit norepinephrine release from the adrenergic nerve in the dilator muscle. Thus pilocarpine decreases tonus of the dilator muscle and induces the miosis.

Animals↗
PubMed1994

Combined timolol and pilocarpine vs pilocarpine alone and timolol alone in the treatment of glaucoma.

We compared the effects of pilocarpine 4% alone, timolol 0.5% alone, and a combination of timolol 0.5% and pilocarpine 4% in the treatment of glaucoma. We treated 43 patients with glaucoma using each drug and then with the combination of drugs for four weeks each. Only patients with a morning intraocular pressure of at least 24 mm Hg without treatment were included. The patients were examined, after one and four weeks of treatment with pilocarpine, timolol, or combined timolol 0.5% and pilocarpine 4%, before the morning dose and at two and five hours after it. At the end of the study, the mean reduction in intraocular pressure from baseline was 9.2 +/- 5.1 mm Hg (28.5% +/- 12.7%) with combined timolol 0.5% and pilocarpine 4%, 5.6 +/- 3.6 mm Hg (17.6% +/- 9.7%) with pilocarpine, and 7.5 +/- 5.0 mm Hg (21.2% +/- 12.6%) with timolol. Intraocular pressure was consistently lower with the combination treatment than with timolol or pilocarpine alone. We believe that this combined solution of timolol-pilocarpine is a valuable contribution to the treatment of open-angle glaucoma.

Administration, Topical↗
PubMed1998

Different effects of pH on the permeation of pilocarpine and pilocarpine prodrugs across the isolated rabbit cornea.

Ocular absorption of pilocarpine and many other ophthalmic drugs can be improved by prodrug derivatization. For stability and solubility reasons basic prodrugs must be formulated at acidic pH, which may affect the corneal drug permeability. We studied the effects of pH on in vitro permeation of pilocarpine, pilocarpic acid benzyl diester prodrugs [O-propionyl (I) and O-valeryl (II)] and O,O'-(1, 4-xylylene) bispilocarpic acid diester prodrugs [O,O'-diacetyl (III), O,O'-dipropionyl (IV) and O,O'-divaleryl (V)] through albino rabbit cornea. Reversed-phase high-performance liquid chromatography was used to assay pilocarpine and its prodrugs. The permeability coefficient for pilocarpine decreased more than three times, from 2. 8x10-6 cm/s to 0.9x10-6 cm/s, when the pH was decreased from 7.65 to 5.5. At pH 7.65 permeability of pilocarpine improved several fold with delivery as prodrugs. Acidic pH (5.5, 6.0) affected to a different extent the corneal permeability of pilocarpine given as prodrugs. Consequently, the rank order of the corneal permeabilities among the compounds was different at various pH values. The effect of pH was greatest (an order of magnitude) for prodrugs with intermediate lipophilicity (I, III, IV), while pH had only minor or no effect on permeability of the most lipophilic prodrugs (II, V). In conclusion, the effect of pH on pilocarpine delivery as prodrug is dependent on prodrug structure and the advantage gained with prodrugs relative to pilocarpine is dependent on formulation pH.

Animals↗
PubMed1986

Pilocarpine prodrugs. II. Synthesis, stability, bioconversion, and physicochemical properties of sequentially labile pilocarpine acid diesters.

Various novel diesters of pilocarpic acid were synthesized and evaluated as prodrug forms for pilocarpine with the aim of improving the ocular delivery characteristics of the drug. The pilocarpic acid monoesters previously studied cyclized spontaneously to pilocarpine in aqueous solution and although they showed enhanced corneal permeability when compared with pilocarpine these monoesters suffered from poor solution stability. The present study shows that this problem can be totally overcome by blocking the free hydroxyl group in the monoesters. Diesters of pilocarpic acid were obtained by esterification of this group. Such compounds were found to possess a high stability in aqueous solution (shelf lives of more than 5 years at 20 degrees C were estimated) but at the same time were readily converted to pilocarpine under conditions simulating those occurring in vivo through a sequential process involving enzymatic hydrolysis of the O-acyl bond followed by spontaneous lactonization of the intermediate pilocarpic acid monoester. Rate data are given for the conversion of the diesters in human plasma and in various rabbit eye homogenates. The pH-solubility profile was derived for a diester and lipophilicity parameters were determined for the compounds. All diesters were markedly more lipophilic than pilocarpine and the corresponding pilocarpic acid monoesters. The results suggest that pilocarpic acid diesters may be potentially useful pilocarpine prodrugs as they combine a high solution stability with an adequate rate of conversion to pilocarpine under in vivo conditions.

Animals↗
PubMed1996

Serum pilocarpine esterase activity and response to oral pilocarpine.

Pilocarpine is used orally to treat xerostomia but patients vary widely in their response and ability to tolerate this drug. To elucidate the potential pharmacokinetic contribution of serum to this variability, the enzymatic hydrolysis of pilocarpine in human serum in vitro was investigated using a stability indicating HPLC assay. The reaction at 37 degrees C follows Michaelis-Menten kinetics (K(m) = 2.78 +/- 0.48 mmol/liter, Vmax = 79 +/- 13 nmol min-1 ml 1; n = 5) and produces pilocarpic acid as the only detectable product. The distribution of pilocarpine esterase activity in a group of healthy young adults at age 21 (n = 163; 87 males, 76 females) was examined by incubating serum samples with pilocarpine (10 mmol/ liter) at 37 degrees C for 60 min. The distribution was positively skewed and ranged from 4 to 132 nmol min-1 ml-1 with a mean value of 55 +/- 23 nmol min-1 ml 1. The means for males and females were not significantly different. Similar measurements in xerostomia patients undergoing treatment with oral pilocarpine showed that those with higher serum esterase activity tolerated pilocarpine well and tended to require higher doses for relief of xerostomia, whereas those with low activity were sensitive to the adverse effects of the drug and were adequately treated with a lower dose. The results suggest that at least some of the variability in response to oral pilocarpine is due to differences in serum pharmacokinetics.

Adult↗
PubMed1987

The functional anatomy and pathology of lithium-pilocarpine and high-dose pilocarpine seizures.

Subcutaneous treatment of rats with low doses of lithium and pilocarpine or a high dose of pilocarpine results in a severe seizure--brain damage syndrome. Rats thus treated were studied with multiple-depth electrodes, quantitative [14C]2-deoxyglucose autoradiography, and light and electron microscopy. Rats receiving lithium-pilocarpine did not differ from high-dose pilocarpine rats in behavioral, electrographic, metabolic or histopathological findings, but lithium-pilocarpine reproduced the syndrome more reliably and with a lower acute mortality rate. Organized electrographic seizure activity developed just prior to the onset of behavioral forelimb clonus and appeared to originate from ventral forebrain in the vicinity of the ventral pallidum and/or nucleus accumbens. From these sites activity spread rapidly to involve other regions. Once initiated, electrographic seizures persisted for hours. Increased glucose utilization was found in most brain regions during the period of continuous seizure activity. The greatest increases were found in the ventral pallidum, globus pallidus, hippocampus, entorhinal cortex, amygdala, lateral septum, substantia nigra, ventrobasal and mediodorsal thalamus and frontal motor cortex. Animals sustaining seizures displayed a disseminated pattern of neural degeneration not involving globus pallidus or ventral pallidum but otherwise coinciding with the above pattern of enhanced glucose utilization. No consistent correlation was observed between the pattern of brain damage and known regions of high muscarinic cholinergic receptor density. Ultrastructurally, the cytopathological changes, like those associated with various other sustained seizure syndromes, resemble the excitotoxic type of damage glutamate is known to cause. This seizure-brain damage syndrome and that induced by systemic kainic acid appear to be similar in behavioral but not in electrophysiological or metabolic manifestations. During kainic acid seizures, electrographic changes are first recorded in the hippocampus while they are first detected in the ventral forebrain region in pilocarpine seizures. Pilocarpine also induced metabolic activation of ventral forebrain sites not activated by kainic acid. The cytopathology associated with the two syndromes is identical in type but not in pattern, the cholinergic model being characterized by much greater neocortical and slightly less hippocampal damage. Further study of these cholinergic models may provide new insights into the roles of the major excitatory neurotransmitter systems (cholinergic and glutamergic) in limbic epilepsy.

Animals↗
PubMed2004

How much pilocarpine contaminates pilocarpine-induced tick saliva?

Pilocarpine is often applied or injected into ticks to induce salivation, and the resulting saliva used to test for various pharmacological, biochemical and immunological activities. To measure the amount of pilocarpine in pilocarpine-induced tick saliva, an HPLC-MS/MS method, based on capillary strong cation exchange chromatography online with an ion trap mass spectrometer, was used to measure pilocarpine in the pg to ng range. Results indicate large concentrations of pilocarpine in Ixodes scapularis Say and Amblyomma americanum (Linnaeus) (Acari: Ixodidae) saliva, ranging from 3 to 50 mm. Due to the known effects of pilocarpine on smooth muscle and immune cells, appropriate controls are proposed and discussed for proper interpretation of results using this saliva preparation.

Animals↗
PubMed1979

Piloplex, a new long-acting pilocarpine polymer salt. B: Comparative study of the visual effects of pilocarpine and Piloplex eye drops.

Induced accommodation and changes in vision (distance and near) were measured monocularly and binocularly in 9 young healthy volunteers in a double blind study after administering to them pilocarpine hydrochloride 4%, Piloplex 3.4, and saline eye drop instillations. Piloplex 3.4, a new long-acting pilocarpine polymer salt, and pilocarpine hydrochloride 4% (both contain equal amounts of pilocarpine-3.4%) induced changes in vision and accommodation. These changes were greater with pilocarpine hydrochloride than with Piloplex. The maximum changes occurred half an hour after instillation and the effect vanished after an additional period up to 3 hours. The changes were greater when measured monocularly than binocularly. Piloplex initiates a prolonged hypotensive effect which lasts for 12 hours. Patients with glaucoma are thus able to use Piloplex on a twice-daily schedule. Consequently, visual disturbances occur only once a day in contrast to pilocarpine hydrochloride given 4 times a day, which induces 3 visual disturbances during the day.

Accommodation, Ocular↗
PubMed1997

A comparative study of Ocusert Pilo 40, intensive pilocarpine and low-dose pilocarpine in the initial treatment of primary acute angle-closure glaucoma.

Acetazolamide and pilocarpine have a central role in the initial management of primary acute angle closure glaucoma (PACG), but there is no consensus concerning their mode of delivery, as borne out by a recent survey of senior UK ophthalmologists reported below. Ocusert Pilo 40 was developed to remain in situ releasing pilocarpine for up to one week. In view of its potential advantages, a trial of Ocusert Pilo 40's efficacy in PACG was conducted. In two separate controlled studies, eyes diagnosed with PACG were randomised to receive Ocusert Pilo 40, and either an intensive pilocarpine regimen or a low-dose pilocarpine treatment. All patients also received Diamox 500 mg i.v. Two hours after starting topical treatment, the study was terminated and ocular and systemic response to treatment and the eventual outcome were assessed. In both studies, intravenous Diamox caused a fall of intraocular pressure (IOP) within 30 min. Over the treatment period, a comparable reduction in IOP was seen in the Ocusert-treated, the intensive-pilocarpine-treated, and the low-dose-pilocarpine-treated groups. No damage to the corneas were observed.

Acetazolamide↗
PubMed1979

[Pilocarpin eye drops with a novel Pilocarpin polymeric salt (author's transl)].

A new pilocarpin salt was obtained by chemically linking pilocarpin to a polymere substance. By galenic processing to the respective emulsion, eye drops containing this pilocarpin salt were produced, which enable a retarded pilocarpin delivery in vitro. With respect to glaucoma therapy, clinical tests showed that frequency of application can considerably be reduced. In the present investigations on a collective of 30 normal volunteers the effect of a commercial aqueous pilocarpin solution on the IOP, pupillary diameter and accommodation was compared with that of the novel pilocarpin drops.

Adult↗
PubMed1986

Stability of pilocarpine hydrochloride and pilocarpine nitrate ophthalmic solutions submitted by U.S. hospitals.

The stability of pilocarpine hydrochloride and pilocarpine nitrate ophthalmic solutions stored in hospital pharmacies across the United States was studied. Through a voluntary drug stability program, FDA selected 252 samples (representing 11 manufacturers) from pharmacies representing an adequate cross section of the country. The samples were analyzed for strength, identification, pH, and isopilocarpine and pilocarpic acid impurities. All samples of pilocarpine nitrate met USP requirements. Eight samples of pilocarpine hydrochloride had tablets that exceeded the USP upper limit for strength. All of these samples were in 1- and 2-mL bottles. The amount of isopilocarpine found ranged from 1 to 6.4%, and the amount of pilocarpic acid from 1.5 to 10.1%. Although pilocarpine salts in ophthalmic solution decompose into isopilocarpine and pilocarpic acid under various conditions of storage, an amount of pilocarpine is maintained that is within the compendial limits. However, there is a problem of evaporation from some of the 1- and 2-mL containers in which this product is supplied.

Drug Contamination↗
PubMedDate not supplied

Comparison of two fixed beta-blocker-pilocarpine combinations. The Carteolol-Pilocarpine Study Group.

PURPOSE: To compare the efficacy and safety of a newly developed ophthalmic solution containing carteolol 2% and pilocarpine (2% (CBS341A) with a timolol 0.5% and pilocarpine 2% fixed combination. PATIENTS AND METHODS: A randomized, double-masked, multicenter study was conducted in 209 patients with primary open-angle glaucoma or ocular hypertension, whose intraocular pressure (IOP) was higher than 21 mm Hg on bet-blocker twice a day alone. The test medications were administered twice daily for 4 months. IOP was measured at 9 and 11 a.m. at the beginning of the study (with beta-blocker alone) and after one and four months of treatment. Adverse effects were recorded. RESULTS: Both combinations caused a similar, statistically significant decrease in IOP. At four months, in the CBS341A group a 2.4 mm Hg (9%) reduction in IOP was achieved at 9 a.m. and 4.1 mm Hg (17.3%) at 11 a.m. compared with respectively 3 mm Hg (11%) and 4.5 mm Hg (19.5%) in the timolol-pilocarpine group. No statistical difference was observed between the two groups in safety and efficacy. CONCLUSIONS: The carteolol-pilocarpine combination appears as safe and as effective as the timolol-pilocarpine combination in the medical treatment of primary open-angle glaucoma or ocular hypertension.

Adrenergic beta-Antagonists↗
PubMed1979

Pilocarpine medication in open-angle glaucoma. A study using pilocarpine eyedrops and an ocular therapeutic system.

Two modes of topical pilocarpine therapy were applied to sixteen patients with open-angle glaucoma. A pilocarpine drop medication (2% solution four times daily) was compared to a constant and continuous supply of pilocarpine by a therapeutic delivery system (Ocusert P-40). The pressure reducing efficiency was studied in the morning and in the following four hour period of an ordinary drop medication regimen. The results indicate about equal pressure reducing properties in both high and low pre-treatment pressure values. However, compared to pilocarpine drops, we found a statistically significant lower pressure in the morning after the Ocusert unit, especially in glaucomatous eyes with high pre-treatment pressure.

Administration, Topical↗
PubMed1989

Timolol-pilocarpine combined vs timolol and pilocarpine given separately.

In a controlled, double-observer, multicenter study, we compared the effect of a fixed combination of timolol 0.5%-pilocarpine 4% twice a day with that of timolol 0.5% twice a day plus pilocarpine 4% three times a day in 80 patients with open-angle glaucoma whose intraocular pressure was greater than 21 mm Hg on timolol 0.5% twice a day alone. Administered twice daily, the combination drug lowered intraocular pressure as effectively as concomitant treatment with timolol twice a day and pilocarpine three times a day. No statistically significant differences in reduction of intraocular pressure were found between the two groups nor were any unexpected side effects observed.

Blood Pressure↗
PubMed1997

Inhibitory action of a calcium channel blocker (nimodipine) on seizures and brain damage induced by pilocarpine and lithium-pilocarpine in rats.

The present work studied the effect of a calcium channel blocker (nimodipine) on rat behavioural changes and brain lesions observed after seizures induced by high doses of pilocarpine (400 mg/kg, s.c.; P400), and the association of lithium (3 mEq/kg, i.p., daily during 7 days) plus pilocarpine (a single dose of 15 mg/kg, s.c.) administered 24 h after the last injection of lithium. In the P400 model, nimodipine (5 or 10 mg/kg, i.p.) inhibited convulsions, status epilepticus, and significantly decreased the percentage of death and cerebral changes (Mann-Whitney, P = 0.0057). In the lithium-pilocarpine (Li-Pi) induced seizures, nimodipine even increased convulsive action and did not interfere with brain lesions. The results suggested that a calcium channel mechanism is involved in the P400 induced seizures, and that there is a difference in the physiopathology of epileptic seizures and brain damage induced by either P400 and Li-Pi models.

Animals↗
PubMed1976

[Pilocarpine as a diagnostic agent for early recognition of a tendency to glaucoma. (Comparable results between Hollwich's pilocarpine-test and tonography) (author's transl)].

In a group of 20 patients Hollwich's pilocarpine-test and tonography were performed repeatedly at regular intervals, for diagnostic purposes. The results of the pilocarpine-test were compared with those of tonography. Hence it was shown, that the pilocarpine-test performed at the peak of the daily pressure curve, gives comparable results to tonography and hence can be useful when glaucoma suspicion exists in the eye-doctor's surgery.

Glaucoma↗