Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “PILOCARPINE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 379 records · Page 21Linked to original sources
PubMed1976

Pilocarpine therapy in glaucoma: effects on anterior chamber depth and lens thickness in patients receiving long-term therapy.

The effect of pilocarpine hydrochloride on the anterior chamber depth and lens thickness was measured in 20 eyes of patients with chronic open-angle glucoma who were receiving long-term glaucoma therapy with pilocarpine. Measurements were made with high-resolution ultrasonic biometry. This study demonstrated that regardless of their age (58.4 years, average) and the fact that they had been regularly using pilocarpine from two to four times a day, 85% of these patients demonstrated narrowing of the anterior chamber (AC) depth (average, 0.19 mm) and thickening of the lens (average, 0.21 mm) with each instillation of pilocarpine. In approximately 15% of eyes, a repeatable deepening of the AC depth and flattening of the lens was noted.

Administration, Topical↗
PubMed1977

Experimental hyphema clearance in rabbits. Drug trials with 1% atropine and 2% and 4% pilocarpine.

The effect of topical 1% atropine sulfate, 2% pilocarpine hydrochloride, and 4% pilocarpine hydrochloride on the clearance rate of RBCs labeled with chromium 51 (51Cr) that were injected into the anterior chamber of rabbits was determined by monitoring sequential radioactivity counts. Counts were made directly over the anterior chamber. One eye of each animal was treated with either 1% atropine, 2% pilocarpine, or 4% pilocarpine, and the other eye served as a control. None of these drugs significantly altered the clearance rate of 51Cr-labeled RBCs injected into the anterior chamber.

Animals↗
PubMed1998

Hippocampal AMPA and NMDA mRNA levels correlate with aberrant fascia dentata mossy fiber sprouting in the pilocarpine model of spontaneous limbic epilepsy.

There is considerable controversy whether aberrant fascia dentata (FD) mossy fiber sprouting is an epiphenomena related to neuronal loss or a pathologic abnormality responsible for spontaneous limbic seizures. If mossy fiber sprouting contributes to seizures, then reorganized axon circuits should alter postsynaptic glutamate receptor properties. In the pilocarpine-status rat model, this study determined if changes in alpha amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) and n-methyl-D-aspartic acid (NMDA) receptor subunit mRNA levels correlated with mossy fiber sprouting. Sprague-Dawley rats were injected with pilocarpine (320 mg/kg; i.p.) and maintained in status epilepticus for 6 to 8 hours (pilocarpine-status). Rats were killed during the: (1) latent phase after neuronal loss but before spontaneous limbic seizures (day 11 poststatus; n = 7); (2) early seizure phase after their first seizures (day 25; n = 7); and (3) chronic seizure phase after many seizures (day 85; n = 9). Hippocampi were studied for neuron counts, inner molecular layer (IML) neo-Timm's staining, and GluR1-3 and NMDAR1-2b mRNA levels. Compared with controls, pilocarpine-status rats in the: (1) latent phase showed increased FD GluR3, NMDAR1, and NMDAR2b; greater CA4 and CA1 NMDAR1; and decreased subiculum GluR1 hybridization densities; (2) early seizure phase showed increased FD GluR3, increased CA1 NMDAR1, and decreased subiculum NMDAR2b densities; and (3) chronic seizure phase showed increased FD GluR2; increased FD and CA4 GluR3; decreased CA1 GluR2; and decreased subiculum GluR1, GluR2, NMDAR1, and NMDAR2b levels. In multivariate analyses, greater IML neo-Timm's staining: (1) positively correlated with FD GluR3 and NMDAR1 and (2) negatively correlated with CA1 and subiculum GluR1 and GluR2 mRNA levels. These results indicate that: (1) hippocampal AMPA and NMDA receptor subunit mRNA levels changed as rats progressed from the latent to chronic seizure phase and (2) certain subunit alterations correlated with mossy fiber sprouting. Our findings support the hypothesis that aberrant axon circuitry alters postsynaptic hippocampal glutamate receptor subunit stoichiometry; this may contribute to limbic epileptogenesis.

Animals↗
PubMedDate not supplied

Age-related differences in ophthalmic drug disposition I. Effect of size on the intraocular tissue distribution of pilocarpine in albino rabbits.

It has previously been documented that substantially different aqueous humour drug levels are observed in rabbits of different ages when the same dose of pilocarpine is instilled into the eye. Also, it has been shown that the aqueous humour volume ratio for rabbits of different ages can be used to predict aqueous humour levels of pilocarpine attained after topical dosing. In the present study, concentrations of pilocarpine in the cornea, aqueous humour, iris-ciliary body, lens, and vitreous humour were determined in both 20-day old and 60-day old rabbits following the topical administration of identical doses of drug. For tissues other than the aqueous humour and iris-ciliary body, consideration of only tissue size differences between rabbits of different ages will not suffice to explain the observed differences in pilocarpine concentration. Any attempt to develop rational age-related dosage modifications for ophthalmic drugs must include a consideration of functional and developmental differences as well as size effects.

Aging↗
PubMed2003

Loss of interneurons innervating pyramidal cell dendrites and axon initial segments in the CA1 region of the hippocampus following pilocarpine-induced seizures.

In the pilocarpine model of chronic limbic seizures, vulnerability of GABAergic interneurons to excitotoxic damage has been reported in the hippocampal CA1 region. However, little is known about the specific types of interneurons that degenerate in this region. In order to characterize these interneurons, we performed quantitative analyses of the different populations of GABAergic neurons labeled for their peptide or calcium-binding protein content. Our data demonstrate that the decrease in the number of GAD mRNA-containing neurons in the stratum oriens of CA1 in pilocarpine-treated rats involved two subpopulations of GABAergic interneurons: interneurons labeled for somatostatin only (O-LM and bistratified cells) and interneurons labeled for parvalbumin only (basket and axo-axonic cells). Stratum oriens interneurons labeled for somatostatin/calbindin or somatostatin/parvalbumin were preserved. The decrease in number of somatostatin- and parvalbumin-containing neurons was observed as early as 72 hours after the sustained seizures induced by pilocarpine injection. Many degenerating cell bodies in the stratum oriens and degenerating axon terminals in the stratum lacunosum-moleculare were observed at 1 and 2 weeks after injection. In addition, the synaptic coverage of the axon initial segment of CA1 pyramidal cells was significantly decreased in pilocarpine-treated animals. These results indicate that the loss of somatostatin-containing neurons corresponds preferentially to the degeneration of interneurons with an axon projecting to stratum lacunosum-moleculare (O-LM cells) and suggest that the death of these neurons is mainly responsible for the deficit of dendritic inhibition reported in this region. We demonstrate that the loss of parvalbumin-containing neurons corresponds to the death of axo-axonic cells, suggesting that perisomatic inhibition and mechanisms controlling action potential generation are also impaired in this model.

Animals↗
PubMed2003

Increased levels of acidic calponin during dendritic spine plasticity after pilocarpine-induced seizures.

We have previously shown that, in HEK 293 cells, overexpression of acidic calponin, an actin-binding protein, induces remodeling of actin filaments, leading to a change in cell morphology. In addition, this protein is found in dendritic spines of adult hippocampal neurons. We hypothesized that this protein plays a role in regulating actin-based filaments during dendritic spine plasticity. To assess this hypothesis, the pilocarpine model of temporal lobe epilepsy was selected because an important reorganization of the glutamatergic network, which includes an aberrant sprouting of granule cell axons, neo-synaptogenesis, and dendritic spine remodeling, is well established in the dentate gyrus. This reorganization begins after the initial period of status epilepticus after pilocarpine injection, during the silent period when animals display a normal behavior, and reaches a plateau at the chronic stage when the animals have developed spontaneous recurrent seizures. Our data show that the intensity of immunolabeling for acidic calponin was clearly increased in the inner one-third of the molecular layer of the dentate gyrus, the site of mossy fiber sprouting, and neo-synaptogenesis, at 1 and 2 weeks after pilocarpine injection (silent period) when the reorganization was taking place. In contrast, in chronic pilocarpine-treated animals, when the reorganization was established, the levels of labeling for acidic calponin in the inner molecular layer were similar to those observed in control rats. In addition, double immunostaining studies suggested that the increase in acidic calponin levels occurred within the dendritic spines. Altogether, these results are consistent with an involvement of acidic calponin in dendritic spine plasticity.

Animals↗
PubMed1979

Vehicle effects on ocular drug bioavailability III: Shear-facilitated pilocarpine release from ointments.

Pilocarpine release from water-in-oil emulsion ointments was studied in vitro and in vivo, using albino rabbits. Pilocarpine release from the vehicle to the ocular fluids was dependent on shear, i.e.,blinking, and the dosing system emulsifying efficiency. A mechanical shearing component was vital for correlating corneal drug penetration and the in vitro pilocarpine release pattern. Simple diffusion studies with the vehicles did not predict drug in vivo release, but the ointment systems were all superior to an aqueous pilocarpine solution. Incorporation of a mechanical shearing component to mimic blinking gave good correlation of in vitro and in vivo results. Also, increasing the vehicle emulsifying efficiency by surfactant addition decreased shear-facilitated drug release and in vivo performance. Finally, increasing the internal aqueous phase volume fraction decreased in vivo performance and was linked to the influence of effective drug concentration in the vehicle.

Animals↗
PubMed1980

High-performance liquid chromatographic determination of pilocarpine in aqueous humor: derivatization by quaternization of methylimidazole tertiary amine group.

A derivatization procedure and a high-performance liquid chromatographic (HPLC) method of analysis for pilocarpine are described. The method is based on the quaternization of the 3'-tertiary amino group of the methylimidazole ring of pilocarpine with p-nitrobenzyl bromide. The HPLC system employs and RP-ODS column with a methanol-water mobile phase containing octanesulfonate as an ion-pairing agent. The sensitivity of the method permits the analysis of pilocarpine in biological fluids such as aqueous humor. The method is selective for pilocarpine in the presence of isopilocarpine. Its applicability to the analysis of aromatic heterocyclic and alkyl tertiary amines is demonstrated.

Animals↗
PubMed1980

Complexes between pilocarpine and cobalt(II), nickel(II), copper(II), and zinc(II) ions.

The properties of pilocarpine as a ligand toward the halides of cobalt(II), nickel(II), copper(II), and zinc(II) were investigated. Pilocarpine behaved as a monodentate ligand, giving rise to compounds with the general formula methyl(pilocarpine)2X2. The coordinating geometry at the metal ion was pseudotetrahedral in every case. PMR studies showed that the pyridine-type nitrogen of the imidazole ring of pilocarpine was the donor atom of the ligand.

Cobalt↗
PubMed1981

Analysis of pilocarpine and isopilocarpine in ophthalmic solutions by normal-phase high-performance liquid chromatography.

A normal-phase high-performance liquid chromatographic separation for pilocarpine and isopilocarpine was developed which is suitable for the routine analysis of ophthalmic preparations. The method utilizes a column packed with 5-micron silica with a mobile phase of hexane-2% ammonium hydroxide in 2-propanol (70:30). Peak detection is by UV at 220 nm. It is suggested that a partition separation mechanism is involved rather than adsorption. A separation factor (alpha) of 1.17 was obtained with a relative separation (Rs) of 2.13. Column lifetimes were typically 6-8 months with daily use. Several standard pilocarpine-isopilocarpine mixtures and five commercially available ophthalmic solutions from different manufacturers were analyzed. The method was specific for pilocarpine and isopilocarpine in the presence of each other and pilocarpine acid and is a significant improvement over the nonspecific colorimetric methods of analysis.

Chromatography, High Pressure Liquid↗
PubMed1981

Analysis of pilocarpine and isopilocarpine in ophthalmic solutions by UV spectrophotometry-polarimetry.

An improved analytical method was developed that simultaneously quantitates pilocarpine and isopilocarpine in the presence of each other and pilocarpic acid. Pilocarpine and isopilocarpine are first separated from any pilocarpic acid present in the sample by eluting with water-washed chloroform through a column packed with acid-washed diatomaceous earth. The concentrations of pilocarpine and isopilocarpine then are determined by a combination of UV spectrophotometric and polarimetric measurements. UV absorbance is measured at the absorption maximum (215 nm), and optical rotation is measured at the 254-nm line of mercury. Standard curve and standard recovery data are presented. The method is applicable to several commercially available ophthalmic solutions of pilocarpine and is compared to both the USP colorimetric method and a high-performance liquid chromatographic method.

Magnetic Resonance Spectroscopy↗
PubMed1986

Pilocarpine prodrugs I. Synthesis, physicochemical properties and kinetics of lactonization of pilocarpic acid esters.

Various alkyl and aralkyl esters of pilocarpic acid were synthesized and evaluated as prodrug forms for pilocarpine with the purpose of improving the ocular bioavailability of pilocarpine through increased corneal membrane permeability. The esters were found to undergo a quantitative cyclization to pilocarpine in aqueous solution of pH 3.5-10, the rate of cyclization being a function of the polar and steric effects within the alcohol portion of the esters. The rates of lactonization increased proportionally with the hydroxide ion activity over the pH range studied which is in accord with a reaction mechanism involving intramolecular nucleophilic attack of alkoxide ion on the ester carbonyl moiety. At pH 7.4 and 37 degrees C, half-times of lactonization ranging from 30 min (p-chlorobenzyl ester) to 1105 min (n-hexyl ester) were observed for the various esters. The esters are markedly more lipophilic than pilocarpine. The results suggested that the pilocarpic acid esters may be potentially useful prodrugs, especially when further derivatized to give in vitro stable pilocarpic acid diesters.

Chemical Phenomena↗
PubMed1983

Evidence against a zinc binding peptide in pilocarpine-stimulated canine prostatic secretions.

Pilocarpine-stimulated canine prostatic secretions were subjected to gel filtration chromatography over Sephadex G-100 and Bio Gel P-4. Free zinc and the zinc in pilocarpine-stimulated canine prostatic secretions were observed to elute in the same fractions from the Sephadex G-100 column. In addition, Sephadex G-100 chromatography could not resolve free zinc from the small peptide bacitracin. However, a column packed with Bio Gel P-4 could resolve free zinc and bacitracin. When pilocarpine-stimulated canine prostatic secretions were chromatographed over the Bio Gel P-4 column, the major portion of the zinc eluted in the same fractions as did free zinc. No zinc was observed in the fractions where the small peptide bacitracin was found to elute. These results indicate that contrary to a previous report, zinc in pilocarpine-stimulated canine prostatic secretions was not bound to an eight amino acid peptide, but, rather, behaved chromatographically like free zinc.

Animals↗
PubMed2003

Down-regulation of mGluR8 in pilocarpine epileptic rats.

Activation of presynaptic metabotropic glutamate receptors (mGluRs) leads to a powerful inhibition of glutamate release from many synaptic terminals throughout the CNS. mGluRs as autoreceptors are believed to provide a negative feedback system that prevents potentially toxic accumulation of glutamate in the extracellular space during synchronous synaptic activity such as epileptic seizures. In this study we analyzed the function of presynaptic mGluR8 on terminals of the lateral perforant pathway in the pilocarpine model of limbic epilepsy. Field excitatory postsynaptic potentials (fEPSPs) recorded in hippocampal slices of rats that developed spontaneous recurrent seizures after pilocarpine-induced status epilepticus (SRS group) showed a significantly reduced sensitivity to Group III mGluR agonists and severe mossy fiber sprouting. The Group III mGluR agonist L(+)-2-amino-4-phosphonobutyric acid (L-AP4, 10 microM) depressed fEPSPs in the SRS group only by 26 +/- 21% compared to 50 +/- 18% in untreated rats. Similarly, the mGluR8 preferring agonist (R,S)-4-phosphonophenylglycine (PPG, 5 microM) was significantly less effective in slices from SRS rats (43 +/- 4% vs. 83 +/- 5%). Concentration-response curves for L-AP4 revealed that the EC(50) values were not different between the control and SRS group (13 +/- 7 microM vs. 9 +/- 9 microM), while the maximal depressing effect was significantly reduced. The remaining depressing effect of L-AP4 in the SRS group could be blocked by the Group III specific antagonists (RS)-alpha-methyl-4-phosphonophenylglycine (MPPG) and alpha-methyl-L-AP4 (MAP4). Rats that did not develop SRS following pilocarpine-induced status epilepticus were indistinguishable from control rats: fEPSPs were highly sensitive to L-AP4 and there was no mossy fiber sprouting. The results show that pilocarpine-induced status epilepticus can lead to a downregulation of mGluR8 and suggest that the condition of SRS is associated with a deteriorated autoregulation of glutamate release.

Animals↗
PubMed1993

Sustained effects of pilocarpine-induced convulsions on brain inositol and inositol monophosphate levels and brain morphology in young and old male rats.

Cerebral inositol and inositol monophosphates, products of phosphoinositide (PI) turnover, and neuronal injury were studied in young (10 weeks) and old (24 months) male Wistar rats after pilocarpine-induced convulsions. The goal was to explore the association between short-term cholinergic convulsions, brain PI signaling, and changes in the brain morphology in the young and the old rats. Pilocarpine caused convulsions in young rats at a dose of 300 mg/kg, whereas a dose of 175 mg/kg was required to obtain the same effect in old rats. A dose of 5 mg/kg of diazepam was used to terminate the convulsions 2 hr after their initiation; the rats were then examined on Day 5 postpilocarpine. Inositol and inositol monophosphate levels were similar in both the young and the old control rats. Pilocarpine-induced convulsions decreased cerebral inositol and increased inositol-1-phosphate in both the young and the old rats. Inositol-4-phosphate was stable in the young rats but increased in the frontal cortex and the hippocampus in the old rats. Delayed neuronal death also occurred in the convulsing rats, i.e., a variable proportion of neurons appeared shrunken with eosinophilic cytoplasm and pyknotic nuclei. The hippocampus was the most severely affected brain area. These results show that old rats are more sensitive than young ones to short-term pilocarpine convulsions, associated with sustained PI turnover, and brain injury. Mechanisms in addition to cholinergic ones are likely to be involved in the prolonged cerebral effects of cholinergic convulsions in rats.

Aging↗
PubMed1984

Effects of pilocarpine, timolol, epifrin and thymoxamine on iris vessels in rhesus monkeys.

In 24 normal eyes of healthy adult rhesus monkeys, the effects of 1% Pilocarpine, 0.5% Timolol, 0.5% levo-epinephrine (Epifrin) and 0.5% Thymoxamine were tested on the iris vessels, intraocular pressure and pupil size. Fluorescein iris angiography and applanation tonometry were performed on the eyes before the use of any drug, and then 2-4 h after topical instillation of each drug; all drugs were used in all the eyes, an interval of one week being left after the use of each drug. The findings of this study suggest that Pilocarpine and Timolol produced vasodilation. Epifrin and Thymoxamine seemed to have no appreciable effect. Pilocarpine produced miosis while other drugs had no significant effect on pupil size. Pilocarpine, Timolol and Epifrin each produced a significant fall in the intraocular pressure. The mechanisms of vascular changes are discussed. The various limitations of fluorescein iris angiography in such a study are stressed.

Animals↗
PubMed1996

Differences in the prejunctional effects of methacholine and pilocarpine on the release of endogenous acetylcholine from guinea-pig trachea.

We investigated the effects of the full muscarinic acetylcholine receptor agonist methacholine and the partial and putatively M2-selective agonist pilocarpine on endogenous acetylcholine release from guinea-pig trachea by use of high-performance liquid chromatography with electrochemical detection. Atropine-induced increases in acetylcholine release were used to monitor the system. Electrical field stimulation (8 V, 30 Hz, 0.5 ms for 5 min)-induced acetylcholine release in the presence of neostigmine, with or without preincubation with choline to maximally enhance acetylcholine output, was increased to about 225% by 0.3 microM atropine, indicating functional autoinhibition. However, methacholine (10 microM) did not affect the acetylcholine release, whereas it was enhanced to 166% by 30 microM pilocarpine. When electrical field stimulation was applied at lower intensity (8 V, 16 Hz, 0.1 ms for 5 min) and in the absence of neostigmine, and increase by 0.3 microM atropine (to 177%) but a decrease of the acetylcholine release by 10 microM methacholine (to 65%) and 30 microM pilocarpine (to 63%) were observed. These results clearly demonstrate (i) that inhibition of evoked endogenous acetylcholine release from prejunctional nerve terminals in guinea-pig trachea can only be demonstrated under conditions of low junctional concentrations of acetylcholine, and (ii) that pilocarpine, as a partial muscarinic agonist, behaves as an antagonist under high junctional concentrations of the neurotransmitter.

Acetylcholine↗
PubMed1995

The additive miotic effects of dapiprazole and pilocarpine.

BACKGROUND: Since dapiprazole on alpha-adrenergic agent, produces miosis by paralyzing the dilator muscle, and pilocarpine, a parasympathetic drug, causes miosis by affecting the sphincter, we speculated that the two drugs might have additive effects. METHODS: The additive miotic actions of pilocarpine 2% and dapiprazole 0.5% were evaluated by comparing the effects of two drugs given together and alone on the reversal of mydriasis induced by tropicamide (0.5%) and phenylephrine (10%) in one eye each of 60 healthy volunteers. RESULTS: Dapiprazole and pilocarpine together induced miosis significantly faster than each drug alone, showing additive effects. CONCLUSION: Co-administration of dapiprazole and pilocarpine at the end of the eye examination will induce fast pupillary constriction, which might be useful in preventing the development of an acute attack of angle-closure glaucoma in patients with anatomically narrow angles.

Adolescent↗