Effect Of Pilocarpine Research Articles

Clinical outcomes of NBF gel application in managing mucositis associated with xerostomia

BackgroundXerostomia, or dry mouth, can be a temporary or persistent symptom resulting from various factors, such as medication use, therapeutic radiation, chemotherapy, autoimmune conditions (e.g., Sjögren’s syndrome), and hormonal imbalances. Xerostomia often leads to associated mucositis, which significantly impacts patients’ quality of life. The nano-bio-fusion (NBF) gingival gel, a gel-type functional toothpaste containing vitamins C, E, propolis, and herbal extracts in a nano-emulsion state, has shown potential in accelerating the healing of oral mucosal lesions.MethodsA total of 127 patients (102 females, 25 males) with persistent xerostomia were treated from 2018 to 2023. Of these, 32 patients were treated exclusively with NBF Gel, while 95 patients received NBF Gel in combination with other medications, such as pilocarpine. The underlying causes of xerostomia included irradiation and chemotherapy (12 patients), medication (40 patients), hormonal imbalance (28 patients), and Sjögren’s syndrome (47 patients). NBF Gel was applied 2–3 times daily to the tongue and oral mucosa. Treatment effectiveness was evaluated through physical examinations and a patient-reported scale ranging from 1 (no improvement) to 10 (complete improvement), focusing on the healing of mucosal lesions rather than saliva production.ResultsBoth treatment groups showed significant improvements in the healing of xerostomia-associated mucositis, particularly in severe cases with visible lesions. Patients treated with NBF Gel reported improved symptoms related to mucosal health, while those who received combination therapy also experienced reduced side effects of pilocarpine due to dose reduction. The most substantial improvements were observed in patients with drug-induced and hormonally-caused xerostomia-related mucositis. No adverse side effects from NBF Gel were reported during the study.ConclusionNBF gingival gel proved to be beneficial in accelerating the healing of mucositis associated with xerostomia, regardless of the underlying cause, including medication use, radiotherapy, chemotherapy, hormonal imbalances, and Sjögren’s syndrome. It presents a promising adjunctive treatment to improve mucosal health and quality of life for patients suffering from xerostomia-associated mucositis.

Transdermal pilocarpine on the skin over salivary glands to increase salivation: an in vivo study

BackgroundHyposalivation is treated using oral cholinergic drugs; however, systemic side effects occasionally lead to discontinuation of treatment. We aimed to investigate the effects of transdermal pilocarpine on the salivary gland skin on saliva secretion and safety in rats.MethodsPilocarpine was administered to rats orally (0.5 mg/kg) or topically on the salivary gland skin (5 mg/body). Saliva volume, the number of sweat dots, and fecal weight were measured along with pilocarpine concentration in plasma and submandibular gland tissues.ResultsSaliva volume significantly increased 0.5 h after oral administration and 0.5, 3, and 12 h after topical administration. Fecal weight and sweat dots increased significantly 1 h after oral administration; however, no changes were observed after topical application. The pilocarpine concentration in the submandibular gland tissues of the topical group was higher than that in the oral group at 0.5, 3, and 12 h of administration.ConclusionsPilocarpine application to salivary gland skin persistently increased salivary volume in rats without inducing sweating or diarrhea. Transdermal pilocarpine applied to the skin over the salivary glands may be an effective and safe treatment option for hyposalivation.

Glial Response and Neuronal Modulation Induced by Epidural Electrode Implant in the Pilocarpine Mouse Model of Epilepsy.

In animal models of epilepsy, cranial surgery is often required to implant electrodes for electroencephalography (EEG) recording. However, electrode implants can lead to the activation of glial cells and interfere with physiological neuronal activity. In this study, we evaluated the impact of epidural electrode implants in the pilocarpine mouse model of temporal lobe epilepsy. Brain neuroinflammation was assessed 1 and 3 weeks after surgery by cytokines quantification, immunohistochemistry, and western blotting. Moreover, we investigated the effect of pilocarpine, administered two weeks after surgery, on mice mortality rate. The reported results indicate that implanted mice suffer from neuroinflammation, characterized by an early release of pro-inflammatory cytokines, microglia activation, and subsequent astrogliosis, which persists after three weeks. Notably, mice subjected to electrode implants displayed a higher mortality rate following pilocarpine injection 2 weeks after the surgery. Moreover, the analysis of EEGs recorded from implanted mice revealed a high number of single spikes, indicating a possible increased susceptibility to seizures. In conclusion, epidural electrode implant in mice promotes neuroinflammation that could lower the seizure thresholds to pilocarpine and increase the death rate. An improved protocol considering the persistent neuroinflammation induced by electrode implants will address refinement and reduction, two of the 3Rs principles for the ethical use of animals in scientific research.

Intracellular signaling pathways involved in the regulation of gene expression by pilocarpine

ObjectivesPilocarpine is commonly used clinically to treat dry mouth. The long-term administration of pilocarpine reportedly improves salivary secretion more effectively than short-term administration. Therefore, we hypothesized that pilocarpine alters gene expression in salivary glands via muscarinic receptor stimulation. This study aimed to investigate the effects of pilocarpine use on gene expression mediated by mitogen-activated protein kinase (MAPK) activity. MethodsThe effects of pilocarpine on gene expression were investigated in rats and human salivary gland (HSY) cells using several inhibitors of intracellular signaling pathways. Gene expression in the rat submandibular gland and HSY cells was determined using reverse transcription–quantitative polymerase chain reaction analysis of total RNA. ResultsIn animal experiments, at 7 days after pilocarpine stimulation, Ctgf and Sgk1 expressions were increased in the submandibular gland. In cell culture experiments, pilocarpine increased Ctgf expression in HSY cells. The mitogen-activated protein kinase kinase inhibitor trametinib, the Src inhibitor PP2, and the muscarinic acetylcholine receptor antagonist atropine suppressed the effect of pilocarpine on gene expression. ConclusionsPilocarpine enhances Ctgf and Sgk1 expressions by activating Src-mediated MAPK activity. Although further studies are required to fully understand the roles of Ctgf and Sgk1, changes in gene expression may play an important role in improving salivary secretions.

Therapeutic Effect of Topical Pilocarpine in Presbyopia Treatment

Purpose: To evaluate the safety, efficacy, and patient satisfaction during the application of low-dose Pilocarpine 1.25% as a treatment option in presbyopia. Study Type: A Prospective Interventional Clinical Trial. Materials and Methods: 120 patients with presbyopia were enrolled in this study, patients ages were between 40 and 55 years. A full history was taken and a detailed ocular examination was done. Measurements of refractive errors, uncorrected distant visual acuity (UCDVA), uncorrected near visual acuity (UCNVA), intraocular pressure, and pupil diameter and iris color assessment were performed before the enrollment and after half an hour, an hour, and three hours from the installation of topical pilocarpine 1.25%. Pilocarpine 1.25% drops were given for a month at a rate of one drop in the morning. Finally, a questionnaire was taken about the extent of satisfaction and reported side effects of the treatment. Results: Our study shows that the application of pilocarpine improved the average UCNVA from J3-J7 to J1-J2 with statistically significant differences (p=0.0001). A slight decrease in the mean UCDVA from 0.7-1.0 to 0.6-0.9 was noticed without statistically significant differences (p=0.09), and a decrease in intraocular pressure with statistically significant differences (p=0.01) was recorded. The self-assessment showed safety and patients were relatively satisfied when using the treatment. Conclusion: The application of low-dose pilocarpine 1.25% drops in a daily dose for the treatment of presbyopia is safe and improves near visual acuity, without a statistically significant effect on uncorrected distant visual acuity, while maintaining its efficacy during the month of the study

A real-life experience of long-term use of pilocarpine in irradiated head and neck cancer patients.

To assess long-term efficacy and side effects of pilocarpine on irradiated head and neck cancer (HNC) patients in both for prevention and treatment of radiation-induced xerostomia (RIX). Retrospective observational study was conducted. Eligibility criteria included irradiated HNC patients who received pilocarpine at least 12 weeks either for prevention (group A) or for treatment (group B) of RIX. We collected the documented Late Effect Normal Tissue Task Force-Subjective, Objective, Management, Analytics subjective/objective grades of RIX before (only group B) and the latest visit for pilocarpine prescription, dosage, side effects, duration of treatment, and the cause of discontinuation. Between December 2007 and June 2022, 182 patients were enrolled including 95 patients (52%) in group A and 87 patients (48%) in group B. Group A patients reported grades 1, 2, 3, and 4 objective RIX in 0%, 7%, 93%, and 0%. Grade 1, 2, and 3 subjective RIX were 57%, 28%, and 15%. All patients in group B had grade 3 both objective/subjective RIX. The overall improvement of objective/subjective RIX was found in 40%/83%. Discontinuation was found in 51% of patients due to tolerable symptoms or deterioration of the patient's status. Based on this retrospective analysis, long-term use of pilocarpine in irradiated HNC appears feasible for both prevention and treatment of RIX.

Prophylactic effect of pilocarpine on acute sialadenitis following radioactive iodine therapy in thyroid cancer patients.

Purpose: Our aim was to evaluate the effect of prophylactic pilocarpine on acute salivary symptoms after radioactive iodine (RAI) therapy in patients with differentiated thyroid cancer. Methods: We enrolled 88 patients (76 women and 12 men; mean age: 47 years; range: 20-74 years) with differentiated thyroid cancer who received RAI. Patients were divided into pilocarpine (51 patients) and control (37 patients) groups. Pilocarpine was given orally, at a dose of 5 mg three times a day, from 2 days before and 12 days after RAI therapy. Symptoms and signs of acute sialadenitis within 3 months of RAI therapy were recorded. Results: During the 3 months after RAI therapy, 13 of the 88 patients (14.7%) developed acute symptomatic sialadenitis (swelling or pain of salivary glands). Acute salivary symptoms were reported by 4 (7.8%) and 9 (24.3%) patients in the pilocarpine and control groups, respectively. Acute salivary symptoms were less frequent in the pilocarpine than control group (p = 0.04), but did not differ by age, sex, or RAI dose (p = 0.3357, p = 0.428, and p = 0.2792). Conclusions: Pilocarpine reduced the likelihood of acute sialadenitis after RAI therapy in patients with differentiated thyroid cancer.

The effect of cardarine on the behavior of rats in a lithium-pylocarpine model of temporal lobe epilepsy

Epilepsy is a serious neuropsychiatric disorder characterized by the occurrence of spontaneous recurrent seizures and linked cognitive, psychoemotional, and social impairments. Objective research showed that up to 30% of epilepsy patients do not respond to current therapeutic interventions, necessitating the development of novel treatment options. In recent years, researchers actively studied the neuroprotective properties of peroxisome proliferator-activated receptor agonists (PPAR α, β/δ, γ). As nuclear transcription factors involved in inflammatory signaling pathways, PPARs play a role in the pathogenesis of neuropsychiatric disorders, such as epilepsy. Various nervous pathology models were used for the investigations. The neuroprotective properties of PPAR γ agonists were reported in epilepsy models, whereas sufficient investigation into PPAR β/δ agonists’ effects is lacking. The aim of this study was to evaluate the effectiveness of the PPAR β/δ receptor agonist cardarine in alleviating behavioral disruptions observed in rats exhibiting temporal lobe epilepsy in response to the lithium-pilocarpine model. The lithium-pilocarpine model is considered one of the most effective experimental models for studying temporal lobe epilepsy in humans. Administration of pilocarpine in animals results in acute seizures, followed by a latent period devoid of seizures. Subsequently, spontaneous recurrent seizures appear, marking the chronic phase of the model. Epilepsy was induced in male Wistar rats that were 7 weeks old, through the administration of pilocarpine, 24 hours after being injected with LiCl (127 mg/kg). The peripheral effects of pilocarpine were negated through the use of methyl bromide-scopolamine (1 mg/kg, administered intraperitoneally 1 hour before pilocarpine). Pilocarpine was administered in fractional doses of 10 mg/kg, every half hour, until the seizures reached at least stage 4 on the Racine scale, with a dose range of 20–40 mg/kg. Following pilocarpine administration, Cardarine was administered intraperitoneally at a dose of 2.5 mg/kg daily for a period of 7 days, with the initial injection taking place 24 hours post-administration. Behavioral tests were conducted during the chronic phase of the model, 2-2.5 months after pilocarpine injection, using several tests, including the Open Field (to measure exploratory behavior, motor activity, and anxiety levels), the Intruder-Resident test (to measure communicative behavior), the Y-maze test (to measure working memory), and the Morris Water Maze (to measure spatial memory in the short and long term). Untreated experimental animals with temporal lobe epilepsy exhibited heightened vertical and horizontal motor activity, increased anxiety in the Open Field test, reduced communicative activity in the Intruder-Resident test, and impaired memory in the Y-maze test and the Morris Water Maze. Cardarine reduced alterations in vertical movement (time of climbing) and anxiety levels (number of grooming behaviors) in the Open Field, hindered short-term memory in the Y-maze, and restrained communicative conduct in the Intruder-Resident test. However, the medication did not impact the rats’ survival rate, body weight changes, overall activity (distance traveled in the Open Field), and damage to learning and long-term memory in the Morris Water Maze. Thus, administration of cardarine partially neutralized behavioral disorders developing in rats in the lithium-pylocarpine model of temporal lobe epilepsy.

Potential antiproliferative and apoptotic effects of pilocarpine combined with TNF alpha in chronic myeloid leukemia cells.

Pilocarpine is a selective M1/M3 agonist of muscarinic acetylcholine receptor subtypes. Muscarinic acetylcholine receptors are G protein-coupled receptors. These receptors are different drug targets. The aim of the present work was to investigate the effect of pilocarpine on the expression of M3 muscarinic acetylcholine receptor, the AChE activity, IL-8 release response, and proliferation in K562 cells, via muscarinic receptor activation.Human chronic myeloid leukemic cell cultures were incubated with drugs. Proliferation assays were performed by BrdU assay. Expression of M3 muscarinic acetylcholine receptor and apoptosis proteins such as bcl, bax, cyt C, and caspases was assessed with the semiquantitative Western blotting method.Pilocarpine inhibits chronic myeloid cell proliferation and M3 muscarinic acetylcholine receptor protein expression. Pilocarpine increases caspase-8 and -9 expression levels, upregulating the proapoptotic protein Bax and downregulating the expression levels of the antiapoptotic protein Bcl-2. The apoptotic activity of pilocarpine is associated with an increase in AChE activity. M3 muscarinic acetylcholine receptors can activate multiple signal transduction systems and mediate inhibitory effects on chronic myeloid K562 cell proliferation depending on the presence of 1% FBS conditions. This apoptotic effect of pilocarpine may be due to the concentration of pilocarpine and the increase in AChE level.Our results suggest that inhibition of cell proliferation by inducing apoptosis of pilocarpine in K562 cells may be one of the targets. M3 selective agonist may have therapeutic potential in chronic myeloid leukemia.

Effect of controlled dynamic sialometry on the secretory function of the parotid glands

Background. It is noted that patients with xerostomia after sialometry may notice a decrease in xerostomia.
 Aim. To study the effect of stimulated sialometry on the quantitative parameters of salivation, to explain the mechanism and reason for such an effect.
 Material and methods. Controlled dynamic parotid sialometry was performed in 22 patients with xerostomia. Saliva was taken with a Lashley capsule (n=44) and a catheter (n=44), stimulated with 1% pilocarpine solution. At the 1st stage, the capsule was on the right, the catheter was on the left, a week later (2nd stage) the catheter was on the right, the capsule was on the left. The amount of saliva (ml) obtained with a capsule was taken as a control indicator, with a catheter as a test indicator, the difference between them determined the rheological state of saliva. The study was approved by the ethical committee. The analysis of indicators in dynamics was carried out separately in the group with a capsule, separately in the group with a catheter. Significance of differences was assessed using Student's t-test. The results were considered significant at p 0.05.
 Results. By the 2nd stage of the study, the sialometry values (ml) obtained using the capsule increased in 13 (69.1%) cases, did not change (n=2; 9.1%) or decreased (n=7; 31.8%) in 9 (40.9%) cases. By the 2nd stage of the study, sialometry values (ml) obtained using a catheter increased in 16 (72.7%) cases, did not change (n=2; 9.1%) or decreased (n=4; 18.2%) in 6 (27.3%) cases. The number of cases with increased secretion was significantly higher than other cases (t=3.385; p 0.001). The dynamics of the rheological state was as follows. A week later, in 7 (31.8%) cases, the indicators of the rheological state of saliva (the difference between the control and test sialometry values of 0.5 ml or more) returned to normal (the difference between the control and test sialometry values of 0.5 ml or less), in 2 (9.1%) cases, the norm was not achieved (t=1.947; p 0.05). Thus, sialometry in the short term can positively influence the secretory function of the salivary glands. However, parasympathetic stimulation of secretory function depletes the number of secretory granules in glandulocytes, which limits the effect of pilocarpine in reducing xerostomia.
 Conclusion. Simultaneous sampling of saliva from the parotid glands with a Lashley capsule (control) and a catheter as a capillary viscometer makes it possible to determine the rheological properties of saliva; the improvement in the rheological properties of saliva after stimulated sialometry is associated with the use of the m-cholinomimetic pilocarpine.

Efficacy of Oral Pilocarpine for Reduction of Post Radiotherapy Xerostomia in Head and Neck Cancer Patients: A Prospective Randomized Institution-based Study

Purpose of study: To evaluate the efficacy and safety of oral pilocarpine concomitantly with radiation treatment for the prevention of radiation induced xerostomia in Head and Neck cancer patients. Material and methods: A prospective randomized study was carried out on 60 histopathological proven squamous cell cancer patients of Head and neck region. All patients received a total radiation dose of 66Gy /33 fraction/6.2 weeks (2Gy/fraction, 5 days/ week) on Telecobalt machine with or without concurrent chemotherapy. The concurrent chemotherapy eligible patients received, weekly chemotherapy courses using cisplatin 30 mg/m2. Patients in the study group received oral pilocarpine 5.0 mg three times a day starting 3 days prior to start of radiotherapy and continued for 3 months post radiotherapy. Patients were evaluated on subjective basis based on Zimmerman Questionnaire and EORTC QLQ HN 35. The statistical analysis was done by Paired sample T test. Results: The average Zimmerman Xerostomia score for all parameters combined was as follows: First assessment -100mm vs 100mm; Second assessment -50mm vs 45mm; Third assessment -59mm vs 52mm; Fourth assessment -64mm vs 57mm, Fifth assessment -71mm vs 68. As per QLQ-HN 35 questionnaire used for assessment of quality of life of patients in both groups, we observed that better scores were obtained in the pilocarpine group in comparison to control group. Conclusion: In the present study, the effectiveness of Pilocarpine given during and 3 months post radiotherapy was observed in terms of better compliance during radiation treatment. Most of the patients had less subjective symptoms with lesser grades of toxicities observed during various phases of assessment post RT.

Safety and efficacy of pilocarpine, cevimeline, and diquafosol compared to artificial tears for the treatment of dry eye: protocol for a systematic review

BackgroundDry eye disease (DED) is a condition that compromises the ocular surface and affects millions of people around the world. In recent years, a scheme has been proposed for the treatment of DED, with the use of artificial tear being the mainstay of treatment. In this scheme, the use of secretagogues is suggested as part of the treatment for patients with moderate to severe affectation. With this systematic review, we aim to evaluate the effectiveness and safety of secretagogues for DED.MethodsElectronic databases will be searched; we will include randomized controlled trials that compare secretagogues and artificial tears. Study inclusion will not be restricted on the basis of language or publication status. We will use Google Translate to assess studies written in languages other than English and Spanish. Identification, evaluation, data extraction, and assessment of risk of bias will be conducted by two authors of the review, a third review author will resolve any disagreement. The outcomes will be the ocular surface disease index score, tear film break-up time, Schirmer test score, VRQoL Score, and tear film osmolarity. We will use the Cochrane Collaboration Risk of Bias 2 (RoB 2) tool for assessing the risk of bias of the included studies.Based on the heterogeneity of the included studies, we will combine the findings in a meta-analysis using a fixed effect model if heterogeneity ≤ 50% or a random effect model if heterogeneity > 50%. If we deem meta-analysis as inappropriate, we will document the reasons and report findings from the individual studies narratively.DiscussionBased on the evidence obtained, we will evaluate the effect of pilocarpine, cevimeline, and diquafosol and compare it to artificial tears on multiple outcome measures.This systematic review aims to determine the efficacy and safety of the secretagogues pilocarpine, cevimeline, and diquafosol to help clinicians in the decision-making process.Trial registrationPROSPERO CRD42020218407.

Activation of M3-AChR and IP3/Ca2+/PKC signaling pathways by pilocarpine increases glycine-induced currents in ventral horn neurons of the spinal cord

Our study aimed to determine the effects of pilocarpine and the mechanisms involving muscarinic acetylcholine receptors (mAChRs) on glycine receptors (GlyRs) in neurons of the spinal cord ventral horn. An enzymatic digestion combined with acute mechanical separation was applied to isolate neurons from the spinal cord ventral horn. Patch-clamp recording was then used to investigate the outcomes of pilocarpine. Our results indicate that pilocarpine increased the glycine currents in a concentration-dependent manner, which was blocked by the M3-AChR selective antagonists 4-DAMP and J104129. Pilocarpine also enhanced the glycine currents in nominally Ca2+-free extracellular solution. Conversely, the enhancement of glycine currents by pilocarpine disappeared when intracellular Ca2+ was chelated by BAPTA. Heparin and Xe-C, which are IP3 receptor antagonists, also totally abolished the pilocarpine effect. Furthermore, Bis-IV, a PKC inhibitor, eliminated the pilocarpine effect. Additionally, PMA, a PKC activator, mimicked the pilocarpine effect. These results indicate that pilocarpine may increase the glycine currents by activating the M3-AChRs and IP3/Ca2+/PKC pathways.

Neuronal Activity Differentially Regulates KCC2 Protein Expression at Distinct Neuronal Maturation Stages

The K+/Cl‐ co‐transporter 2 (KCC2), a protein exclusively expressed in neurons, facilitates the co‐transport of a K+ and a Cl‐ ion across the cell membrane. The developmental shift of GABAA receptor mediated responses from depolarizing to hyperpolarizing is mainly due to a developmental upregulation of KCC2. Moreover, in mature neurons, neuronal activity leads to a decrease in surface expression and phosphorylation of Ser940 residue of KCC2, thereby reducing its activity. KCC2 is additionally phosphorylated at Thr906 and Thr1007, which reduces KCC2 surface expression and thus activity.Given the important role of neuronal activity in regulating KCC2 expression, we sought to investigate the effect of pilocarpine or 4‐aminopyridine (4AP) treatment on KCC2 expression across different maturation stages of neurons using quantitative RT‐PCR, immunocytochemistry (ICC) and immunoblotting. We also investigated the three phosphorylation sites – Ser940, Thr906 and Thr1007 – of KCC2. Immature neurons (day in vitro 4) from embryonic day 18.5 mouse hippocampus were treated with pilocarpine or 4AP (100µM, 60 minutes). The results show that 4AP or pilocarpine treatment has no effect on KCC2 transcript or protein expression, compared to controls. Similarly, ICC and immunoblotting results showed that there was no change in the phosphorylation status of Ser940. ICC results also showed that the phosphorylation status of Thr906 and Thr1007 remained unaltered in immature neurons after pilocarpine treatment.In day in vitro 17 organotypic hippocampal slices cultured from postnatal day 2 mouse pups, immunoblotting showed that treatment with 4AP did not affect KCC2 protein expression. However, in day in vitro 35 organotypic hippocampal slice cultures, 4AP treatment reduced KCC2 whole protein expression.These results demonstrate that neuronal activity has a distinctive effect on KCC2 protein as the neurons mature, suggesting a differential regulation of KCC2 protein at different maturation stages.

Effectiveness of topical pilocarpine in refractory oral lesions of pemphigus vulgaris: Results from an open-label, prospective, pilot study.

The literature suggests a beneficial role of cholinomimetic agents in the treatment of pemphigus. In the present open-label, prospective pilot study, we assessed the effectiveness of topical pilocarpine 2% eye-drops in the treatment of recalcitrant oral lesions of pemphigus. Twenty patients with recalcitrant oral lesions of pemphigus were recruited and instructed to apply pilocarpine 2% eye-drops twice daily on the resistant oral lesions for 180 days. The systemic immunosuppression at the time of inclusion in the present study was continued at the same dose throughout the study duration. The photographs of the lesions were obtained at baseline and an interval of 30 days. The area representing the erosion was measured on clinical photographs using the imageJ software (National Institute of Health). Visual analogue scale and oral health impact profile-14 questionnaire were used to assess the degree of subjective improvement. Anti-desmoglein 1 and 3, and anti-acetylcholine M3 receptor antibodies were measured both in serum and saliva; at baseline and at the completion of the study. Twenty patients were recruited in this pilot study. Mean total duration of illness was 3.4±1.3 years. The mean area of the erosions decreased significantly from 142.01±130.05 mm2 to 44.38±67.78 mm2 at study completion at 180 days (p 0.002, paired t-test). Repeated measures ANOVA demonstrated a significant trend in the reduction of the mean area of the erosions from baseline to day 180 (p 0.002). Mean VAS decreased significantly from 7.2±1.0 at baseline to 5.1±1.9 at day 180 (paired t-test, p 0.001). Mean OHIP-14 decreased significantly from 10.1±2.7 at baseline to 8.4±2.9 at day 180. No significant difference was observed between pre- and post-treatment levels of anti-desmoglein 1, anti-desmoglein 3, and anti-acetylcholine M3 receptor antibodies, in both serum and saliva. The depth component in the erosions could not be measured. An orabase formulation could be used in future studies to facilitate retention of the medication at the site of application. Topical pilocarpine holds potential for the treatment of recalcitrant oral lesions of pemphigus vulgaris. It probably brings about re-epithelialization without imparting any immunomodulatory activity. This article is protected by copyright. All rights reserved.

Pilocarpine-Induced Effects on Salivary Secretion as a Pharmacological Biomarker for Cholinergic Parasympathetic Activation.

Pilocarpine-induced salivary secretion could serve as a nontherapeutic target engagement biomarker in a clinical setting to test the activity of an M3 positive allosteric modulator (PAM). The potentiating effect on the reactivity of the M3 receptor to the agonistic effect of pilocarpine would support the mechanism of action of an M3 PAM in a variety of therapeutic areas. The aim of this study was to determine the optimal pilocarpine dose needed for evaluation of this potentiating effect. Therefore, the effects of pilocarpine on salivary secretion rate and its pharmacokinetics were explored at single doses of 2.5, 5, and 10mg of pilocarpine or placebo. The study also explored the test-retest variability of the pilocarpine-induced effects on salivary secretion. Pilocarpine caused a reproducible, dose-related increase in overall and maximum salivary secretion rate, in line with pilocarpine exposure. Oral doses of pilocarpine from 2.5 to 10mg were safe and well tolerated, consistent with the published safety profile. These results support the use of pilocarpine in single-dose pharmacological challenge studies. The recommended dose for evaluating M3 PAM activity would be between 2.5 and 5mg, showing a small increase in salivary secretion rate with room for further increase due to PAM activation.

The Prophylactic Effects of Metoprolol, Diltiazem, and Pilocarpine on Hypoglycemia-Induced Prolongation of QT Interval.

BackgroundInsulin-induced hypoglycemia has been demonstrated to prolong the corrected QT (QTc) interval. Prolongation of the QTc interval, especially in diabetic patients using insulin, can cause fatal ventricular arrhythmias. The aim of this study was to evaluate the effects of metoprolol, diltiazem, and pilocarpine on hypoglycemia-induced QTc prolongation.MethodsThirty male rats were randomly distributed into the following five groups: Group 1 (1 mL/kg saline, n=6), Group 2 (40 U/kg crystalline insulin + saline, n=6), Group 3 (40 U/kg crystalline insulin + 1 mg/kg metoprolol, n=6), Group 4 (40 U/kg crystalline insulin + 0.8 mg/kg pilocarpine, n=6), and Group 5 (40 U/kg crystalline insulin + 2 mg/kg diltiazem, n=6). Three hours after insulin injection, the blood glucose level was measured in all groups. Blood glucose <40 mg/dl was defined as hypoglycemia. Electrocardiograms (ECG) were taken in lead I (DI), and QTc was calculated by using Bazett’s formula.ResultsGroup 2 (insulin + saline) showed that it had a significantly prolonged QTc interval as compared to the control group (p<0.0001). However, treatments of the rats with metoprolol, pilocarpine, and diltiazem significantly prevented prolongation of the QTc interval as compared to the insulin + saline group (p<0.005, p<0.005, and p<0.01, respectively).ConclusionThe findings of the present study demonstrated the efficacy of metoprolol, pilocarpine, and diltiazem in the prevention of hypoglycemia-induced QTc prolongation in male rats.

Histological Evaluation of The Effect of Pilocarpine on the Lingual Salivary Glands of The Root of the Tongue After X-Ray Irradiation in Rats

Aim: The aim of this study was to evaluate the effect of pilocarpine on the histological changes, induced by exposure to radiation therapy, in the rat’s lingual salivary glands. Subjects and methods: This study was carried on 30 adult male Sprague-Dawley rats weighing 150-250 g. That the rats were divided into 3 groups (10 rats per each). Group I: Control group received neither radiation nor drug. Group II: exposed to a single whole body γ-irradiation at dose of 6 Gray (Gy). Group (3): the rats were injected intraperitoneally by a single dose of pilocarpine hydrochloride (0.2 mg/kg) 90 minute before the exposure of the previous dose of radiation. Results: One week after x-ray radiation the glands demonstrated marked destructive changes. These changes comprise in the form of loss of acinar architecture, and acinar degeneration and atrophy. Pilocarpine administration prior to radiation has decreased, but not completely prevents, the harmful effects of radiation. The radioprotective effect of pilocarpine treatment was manifested by the decreased atrophic changes and the absence of degenerated acinar cells. Conclusion: Administration of pilocarpine can protect, to some extent, the lingual salivary glands against radiation histological damage.

Lactation in large litters influences anxiety, memory, and spreading depression in adult male rats that were chronically subjected to a non-convulsive pilocarpine dose

ABSTRACT Objectives: Unfavorable lactation influences brain excitability and behavioral reactions in adults. Administration early in life of the cholinergic agonist, pilocarpine, even at non-convulsive doses, alters the brain excitability-related phenomenon known as cortical spreading depression (CSD), and produce anxiogenic-like behavior. However, the influence of unfavorable lactation on the CSD- and memory-effects of pilocarpine administration late in life has not been investigated. Herein, we analyzed the ponderal, electrophysiological (CSD), and behavioral effects of chronic treatment with a non-convulsive dose of pilocarpine, in adult rats suckled under favorable and unfavorable conditions. Methods: Wistar rats were suckled in litters with 9 or 15 pups (groups L9 and L15, respectively). A very low dose of pilocarpine (45/mg/kg/day) was chronically administered in mature rats from postnatal day (PND) 69–90. Behavioral tests occurred at PND91 [elevated plus maze (EPM)], PND93 [open field (OF)], and PND94–95 [object recognition memory (ORM)]. CSD was recorded between PND96–120. Results: Pilocarpine-treated rats performed worse in the anxiety and memory tests, and displayed lower CSD propagation velocity when compared with saline-treated controls. In addition, L15 rats showed an increase in the distance traveled and a decrease in the immobility time in the EPM, impaired ORM, and accelerated CSD propagation when compared with L9 rats (p ≤ 0.05). Discussion: These data suggest that sub-convulsive pilocarpine treatment in adult rats can affect behavioral and excitability-related reactions. In addition, unfavorable lactation increases the ambulatory effects of pilocarpine. Further studies should investigate the possible cholinergic molecular mechanisms involved in these effects.

The prophylactic effects of metoprolol, diltiazem and pilocarpine on hypoglycemia-induced prolongation of QT interval

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)