Disease relevance of pilocarpine

• A prospective, randomized, double-blind, placebo-controlled trial was undertaken to test the safety and efficacy of pilocarpine, particularly in reversing the decrease in the production of saliva and other manifestations of xerostomia [1].
• Oral pilocarpine for post-irradiation xerostomia in patients with head and neck cancer [1].
• Intraluminal boluses of 4 mg pilocarpine, or 0.1 mg prostaglandin E2, caused changes of -4.6 mV and -4.5 mV, respectively, in controls; these responses were not seen in patients with cystic fibrosis [2].
• Pilocarpine-induced status epilepticus caused a dramatic and prolonged increase in cell proliferation in the dentate subgranular proliferative zone (SGZ), an area known to contain neuronal precursor cells [3].
• The pilocarpine model of temporal lobe epilepsy was used to study the time-dependent changes in dentate gyrus circuitry after seizures [4].

Psychiatry related information on pilocarpine

• The aggravation of dementia by pilocarpine [5].
• The cholinergic REM sleep induction test with pilocarpine in mildly depressed patients and normal controls [6].
• Enhanced miotic response to topical dilute pilocarpine in patients with Alzheimer's disease [7].
• Pilocarpine decreased slow-wave sleep and EEG delta power during the first nonREM episode more in controls than in patients, and enhanced EEG sigma power equally in both groups [8].
• Mouse-killing and motor activity: effects of chronic delta9-tetrahydrocannabinol and pilocarpine [9].

High impact information on pilocarpine

• Pilocarpine-induced saliva of the tick, Ixodes dammini, inhibited platelet aggregation triggered by ADP and collagen, as well as platelet-aggregation factor [10].
• Likewise, loss of M2 receptor function was demonstrated since the agonist pilocarpine inhibited vagally-induced bronchoconstriction in control but not challenged animals [11].
• In pathogen-free guinea pigs indomethacin (1 mg/kg) did not alter the effect of either gallamine or pilocarpine, thus in pathogen free animals neuronal M2 muscarinic receptors function independently of cyclooxygenase products [12].
• The pilocarpine-induced sweat responses (SR) in the hind foot pads of groups of control and streptozocin diabetic rats, in good (GC) and in poor (PC) glycemic control and with a crossover design after 20 wk of diabetes, were evaluated with the silicone mold sweat test to determine the number of sweat droplets per group of foot pads [13].
• The fall in volume density of the secretory granules produced by pilocarpine and by isoproterenol occurred without any change in the surface-to-volume ratio of the granules [14].

Chemical compound and disease context of pilocarpine

• These include spontaneously seizing models with status epilepticus as the initial precipitating injury (including the kainate, pilocarpine, and electrical stimulation models), kindling, and models of drug refractoriness [15].
• A group of neurons with the characteristics of dentate gyrus granule cells was found at the hilar/CA3 border several weeks after pilocarpine- or kainic acid-induced status epilepticus [16].
• Mast cell degranulation, hepatic glycogen depletion, and hyperglycemia in Compound 48/80 or pilocarpine-treated rats [17].
• Correlation between hypermetabolism and neuronal damage during status epilepticus induced by lithium and pilocarpine in immature and adult rats [18].
• The effects of three single oral doses (25 mg, 50 mg and 100 mg) of amitriptyline and desipramine, and of placebo, were compared on a range of cholinergic functions (resting pupil diameter, pilocarpine-evoked miosis, baseline-sweating, carbachol-evoked sweating, salivation, heart rate) in eight healthy volunteers [19].

Biological context of pilocarpine

• Compound 48/80 produced a marked decrease in mean carotid blood pressure, while pilocarpine produced a slight increase in this parameter [17].
• Salivation in response to pilocarpine stimulation was reduced significantly in both Nhe1(-/-) and Nhe2(-/-) mice, particularly during prolonged stimulation, whereas the loss of NHE3 had no effect on secretion [20].
• Pilocarpine, like muscarinic antagonists, recognized all binding sites with the same affinity but acted as a partial agonist on amylase secretion and 45Ca efflux [21].
• Here we show that the decreased salivary flow rate and increased tonicity of the saliva secreted by Aqp5(-)/- mice in response to pilocarpine stimulation are not caused by changes in whole body fluid homeostasis, indicated by similar blood gas and electrolyte concentrations in urine and blood in wild-type and AQP5-deficient mice [22].
• Likewise, the kinetics of pilocarpine-induced discharge of radioactive material from pancreatic slices pulse-labelled with either 3H-Leu. or 35S-sulphate was compared [23].

Anatomical context of pilocarpine

• Microtubules may be involved in this secretory process because colchicine inhibits the pilocarpine effect [24].
• Principal cells of mouse gallbladder epithelium were subjected to a quantitative electron microscope study after in vivo and in vitro exposure to pilocarpine, noradrenaline, atropine, and phenoxybenzamine [25].
• We examined the chromatin structure of a Balbiani ring (secretory protein gene) in the salivary glands of Chironomus larvae in its hyperactive state after stimulation with pilocarpine [26].
• Isoproterenol and pilocarpine were used to stimulate the parotid gland and the pancreas, respectively [27].
• We used limbic seizures induced in rats by systemic injection of the cholinergic agonist pilocarpine (380 mg/kg; i.p.) to study the neuronal pathways within the basal ganglia that modulate seizure threshold [28].

Associations of pilocarpine with other chemical compounds

• 20 min after heparin or poly-L-glutamate, the effects of both pilocarpine and gallamine on vagally induced bronchoconstriction were restored, demonstrating recovery of M2 receptor function [29].
• In vitro incubation for 30 min with a combination of pilocarpine and atropine extinguished the pilocarpine-induced effect on the secretory granules [25].
• Lesioning the caudate-putamen (by bilateral microinjection of the excitotoxin ibotenate) converted subconvulsant doses of pilocarpine into convulsant ones [28].
• Three hours after the onset of self-sustaining SE (SSSE), induced either by intermittent stimulation of the perforant path for 30 min (PPS) or by injection of lithium and pilocarpine, Gal-IR fibers disappeared in the hilus and remained absent for up to 1 week afterward [30].
• Local application of an excitatory amino acid N-methyl-D-aspartate, into the substantia nigra pars compacta, ventral tegmental area, or retrorubral area, sites of origin of mesostriatal dopaminergic pathways, protects rats against seizures produced by pilocarpine [31].

Gene context of pilocarpine

• To establish the role of AQP5 in sweat secretion, we tested the response of adult mice to s.c. injection of pilocarpine, as visualized by reaction of secreted amylase with iodine/starch [32].
• Although diminished in magnitude, a sweat response to pilocarpine was also noted in TH -/- mice at P21 [33].
• At the chronic stage, i.e. at 2 months after pilocarpine-induced status epilepticus, significant reduction of CCR7-10 expression in CB-, CR- and PV-immunpositive interneurons may suggest the phenotype change of surviving interneurons [34].
• A high dose of pilocarpine (300 mg/kg) caused seizures and lethality in wild-type and M2-M5 knockout mice, but produced neither effect in the M1 knockout mice [35].
• 4. These results suggest that pilocarpine has (i) a high affinity towards phenobarbitone-inducible CYP2A4/5 and CYP2B activities in mouse liver, (ii) a high affinity towards CYP2A6 in human liver microsomes and (iii) a moderate affinity towards CYP3A enzyme(s) in both microsomal preparations [36].

Analytical, diagnostic and therapeutic context of pilocarpine

• When compared with the effect of normal saline in the same rats, intravenous injection of pilocarpine, 10 mg/kg, increased immunoglobulin A concentrations in perfusates from ileal loops (p less than 0.001) [37].
• Affinity-purified, monospecific rabbit antibodies against rat pancreatic alpha-amylase and bovine pancreatic alpha-chymotrypsinogen were used for immunoferritin observations of ultrathin frozen sections of mildly fixed exocrine pancreatic tissue from secretion-stimulated (pilocarpine) rats and from overnight-fasted rats and guinea pigs [38].
• Teenagers and young adults with long-standing pulmonary or digestive symptoms, unexplained cirrhosis, aspermia, or a sibling with cystic fibrosis should be sweat-tested by pilocarpine iontophoresis [39].
• Bilateral microinjections of N-Me-D-Asp into the caudate-putamen, however, protected against limbic seizures induced by pilocarpine (injected systemically), with an ED50 of 0.7 nmol (range 0.5-1.0 nmol) [28].
• Bromodeoxyuridine labeling, in situ hybridization, and immunohistochemistry were used to identify proliferating progenitors and mature DGCs in the adult rat pilocarpine temporal lobe epilepsy model [40].

References