Neostigmine Research Articles

Modified carbon paste sensor for the potentiometric determination of neostigmine bromide in pharmaceutical formulations, human plasma and urine

A novel, simple, rapid, selective and sensitive method for the determination of neostigmine (Ns) ion in its bulk powder, different pharmaceutical dosage forms, and biological fluids (plasma and urine) using four modified carbon paste electrodes was developed. Sensor 1 is based on ion-association Ns-TPB, sensor 2 used Ns-PT, sensor 3 comprises a mixture of (Ns-PT+Ns-TPB) and sensor 4 was constructed using (Ns-PT+β-CD). Solvent mediator 2-NPPE exhibited a proper behavior including Nernstian slope ranging from 61.5±0.5 to 64.5±0.5mV per decade over the pH range of 3.8–10 for the four sensors. Linear responses of Ns within the concentration range 1.0×10−7–1.0×10−2mol/L were obtained. The response time is very short (≤10s) with a detection limit 6.3×10−8M. In flow injection analysis (FIA), sensor 3 shows a Nernstian slope value 75.5±0.5mV per decade within the concentration range of 1×10−6–1×10−2mol/L and with a detection limit 7.5×10−7mol/L. The utility of mixed or additives of β-CD had a significant influence on increasing the sensitivity of sensors 3 and 4 compared to sensors 1 and 2. The sensors were applied for the determination of neostigmine (Ns) ion in its bulk powder, different pharmaceutical dosage forms, and biological fluids (plasma and urine). The results obtained were satisfactory with excellent percentage recovery comparable with official method for the assay based on non-aqueous titration using perchloric acid as a titrant.

Neostigmine product for NMBA reversal approved by FDA

FDA recently approved the marketing of the first neostigmine product for use in reversing the effects of nondepolarizing neuromuscular blocking agents (NMBAs) after surgery. Neostigmine methylsulfate injection has been available for decades, but until May 31 no company had an FDA-approved new drug

The effect of cholinesterase inhibition on liver dysfunction in experimental acute liver failure

IntroductionAcute liver failure (ALF), like sepsis, is associated with an overwhelming activation of the immune response in which hepatic and circulating inflammatory cytokines play a pivotal role. Cholinesterase inhibition has been shown to have anti-inflammatory properties in experimental sepsis. We investigated the role of neostigmine in attenuating d-galactosamine (d-GalN)-induced ALF. MethodsThirty-six female wistar rats were randomly allocated to three groups: a control group, a d-GalN group receiving a single i.p. injection of d-galactosamine (400 mg kg−1 BW) and a neostigmine-treated d-GalN group receiving a single i.p. injection of d-galactosamine followed 24 h later by i.p. injection of neostigmine methylsulfate 0.25% (80 μg kg−1 BW) three times daily for 3 successive days. Rats were sacrificed 24 h after the last injection. Plasma levels of liver transaminases, total proteins, albumin, prothrombin, total bilirubin and hepatic levels of superoxide dismutase and malondialdehyde were measured. Liver expression of cytokines (HMGB-1, TNF-α and IL-10) and histopathology were evaluated. ResultsNeostigmine attenuated liver dysfunction and improved liver synthetic and excretory functions, reduced proinflammatory cytokine HMGB1 (95% CI 0.33–1.09) and TNF-α (95% CI 1.26–2.06) expression compared to d-GalN group (95% CI 2.67–4.73 and 7.33–14.53, respectively, P < 0.001) and increased expression of the anti-inflammatory cytokine IL-10 in liver tissue (95% CI 2.49–4.17 vs 0.04–0.21 in d-GalN group, P < 0.001). Neostigmine also significantly increased antioxidant level, and decreased oxidative burden caused by d-GaIN. ConclusionNeostigmine improved liver function in a rat ALF model through an anti-inflammatory activity.

Effects of arterial carbon dioxide on recovery from rocuronium-induced neuromuscular blockade in anesthetized patients

Background: Respiratory function can be impaired during general anesthesia involving neuromuscular blockers such as rocuronium. However, the magnitude of the problems and the efficacy of their reversal with antagonistic drugs are not known. Objective: To investigate the effects of arterial carbon dioxide (PaCO2) on recovery from rocuronium-induced neuromusuclar blockade with or without antagonism by neostigmine. Methods: Ninety patients were randomly divided into six groups; group I and A, normal PaCO2 (35-45mmHg), group II and B, low PaCO2 (30-35mmHg), group III and C, high PaCO2 (45-50mmHg). The extent of neuromuscular blockade was evaluated by train-of-four (TOF) -watch accelerograph. Anesthesia was induced with intravenouspropofol, fentanyl, and rocuronium 0.6mg/kg. Additional injection of rocuronium 0.15mg/kg per time was given whenever the first twitch of TOF (T1) recovered to 25%. The residual neuromuscular blockade was antagonized with neostigmine 0.02mg/kg in the groups I, II and III, when T1 reached 25%. The duration from T1 25% to 75%was recorded and defined as the recovery index and that from T1 25% to TOFR 0.9 was the recovery time.

Effect of acupuncture on rabbit bladder with urodynamic indexes

ObjectiveTo study the effect of acupuncture on rabbit bladder with urodynamic indexes. MethodsNew Zealand male rabbits were divided into control group, model group, treatment group 1 treated by acupuncture at Shenshu (BL 23) and treatment group 2 treated by acupuncture at Zhongji (CV 3). The urine dynamic parameters through the urethral catheter were detected in each group in order: fluctuation of pressure at filling phase of urinary bladder and flow rate in urination phase, which were used as quantification indexes of urinary bladder function. The urinary bladder abnormal model was prepared by administration of cholinergic stimulant; Regulatory effects of acupuncture at Shenshu (BL 23) and Zhongji (CV 3) on the abnormal state of the urinary bladder were respectively observed. Results1) In the filling phase of urinary bladder and in the urination phase, the intravesical pressure wave in infilling (IPWI) and intravesical discharge rate (IDR) could be respectively recorded. 2) IPWI and IDR could become abnormality by neostigmine methyl sulfate [stability type IPWI: the control group (n=20, 80%) vs the model group (n=15, 14.3%), P<0.01; IDR and time regression equation: the control group (n=20, y=24.3 – 0.878x) vs the model group (n=15, y=40.0 – 5.15x), P<0.01]. 3) Abnormal IPWI's could be normalized respectively by acupuncture at Shenshu (BL 23) and Zhongji (CV 3) [the stability type IPWI wave: the model group (n= 2, 14.3%) vs the treatment group 1 (n=3, 30%), P> 0.05; the instability type IPWI wave: the model group (n=13, 85.7%) in vs the treatment group 2 (n=6, 60%), P>0.05]; 4) Abnormal IDR also could be turned to normality by acupuncture at Shenshu (BL 23) and Zhongji (CV 3), respectively [IDR and the time regression equation: the model group (n=15, y=40.0 – 5.15x) vs the treatment group 1 (n=10, y= 18.9 – 0.499x), P<0.01; the model group (n=15, y= 40.0 – 5.15x) vs the treatment group 2 (n=10, y= 17.5 – 0.251x), P<0.01]. Conclusion1) Urodynamic indexes can be used for study of mechanism of acupuncture effects; 2) The effect of acupuncture in the bladder filling phase is smaller than that in the urination phase; 3) Acupuncture has a very obvious effect on intravesical discharge rate.

Therapeutic efficacy of a preoperative epidural single shot of dexamethasone/levobupivacaine for postoperative analgesia ( a placebo-controlled comparative study against epidural neostigmine/levobupivacaine)

Objectives The aim of the present study was to evaluate the postoperative (PO) outcome of epidural dexamethasone (D) or neostigmine (N) compared with epidural placebo at the time of induction of anesthesia in patients assigned for open abdominal hysterectomy. Patients and methods The study included 90 women classified under ASA I–II randomly allocated to three equal groups according to administration of an epidural adjuvant as only one preemptive shot of epidural injection: group L received plain levobupivacaine 0.1%; group L/D received a combination of levobupivacaine 0.1% and dexamethasone 8 mg; and group L/N received a combination of levobupivacaine 0.1% and neostigmine 500 μg. The intensity of PO pain was measured using a 100 mm visual analog scale (VAS), and rescue analgesia was given when the patient had a VAS score of 40. The duration of analgesia, postoperative nausea and vomiting (PONV), and its frequency and score were monitored. Results Preemptive epidural therapy provided PO analgesia without significant difference until 2 h postoperatively. Until 8 h postoperatively, pain VAS scores were significantly lower in groups L/D and L/N compared with group L; at 10 h postoperatively, pain VAS scores were significantly lower in the L/D group compared with the other groups. The total pain VAS score at the end of 24 h was significantly lower in the L/D group compared with the L/N and L groups, with significantly lower scores in the L/N group compared with group L. The mean duration of PO analgesia was significantly longer in the L/D group compared with groups L/N and L, with significantly longer duration in the L/N group compared with group L. Thirty-nine patients (43.3%) complained of PONV, of whom 19 patients (21.1%) requested for antiemetics with significantly reduced frequency and score in the L/D group compared with the other groups, which showed a nonsignificant difference. Conclusion Single-shot epidural dexamethasone and levobupivacaine is a safe and effective PO analgesic modality for patients assigned for open abdominal hysterectomy, with minimization of PONV frequency and severity.

Pharmacological Evaluation and Docking Studies of 3-Thiadiazolyl- and Thioxo-1,2,4-triazolylcoumarin Derivatives as Cholinesterase Inhibitors

Inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) is considered a promising strategy for the treatment of Alzheimer's disease (AD). This research project aims to provide a comprehensive knowledge of newly synthesized coumarin analogues with anti-AD potential. In the present work a series of 3-thiadiazolyl- and thioxo-1,2,4-triazolylcoumarins derivatives were designed, synthesized, and tested as potent inhibitors of cholinesterases. These compounds were assayed against AChE from electrophorus electricus and rabbit; and BChE from horse serum and rabbit by Ellman's method using neostigmine methylsulphate and donepezil as reference drugs. Some of the assayed compounds proved to be potent inhibitors of AChE and BChE with Ki values in the micromolar range. 4b was found to be the most active compound with Ki value 0.028 ± 0.002 μM and higher selectivity for AChE/BChE. The ability of 4b to interact with AChE was further confirmed through computational studies, in which a primary binding was proved to occur at the active gorge site, and a secondary binding was revealed at the peripheral anionic site. Structure activity relationships of prepared compounds were also discussed.

The impact of acetylcholinesterase inhibitors on the extracellular acetylcholine concentrations in the adult rat brain: A meta‐analysis

In vivo microdialysis has become a key method in investigating the dynamics of different neurotransmitter systems such as acetylcholine in the extracellular fluid. Depending on the sensitivity of the analytical method applied for measuring acetylcholine levels in brain dialysates, acetylcholinesterase (AChE) inhibitors are often used to increase the basal acetylcholine level up to a detectable magnitude. This artificial manipulation of the system questions the outcome of pharmacological studies and has led to a large number of experiments pursuing the appropriate physiological and pharmacological concentration of the AChE inhibitors in a range between 0.01 and 100 μM. However, the complexity of the action of these substances, particularly through the involvement of muscarinic autoreceptors and the induction of an autoinhibitory effect on acetylcholine release, did not allow this quest to be resolved completely and suggests the application of advanced mathematical methods for the evaluation of acetylcholine baseline levels. Here we performed a meta-analysis on published datasets of in vivo microdialysis measurements to assess the concentration-dependent effects of various AChE inhibitors on acetylcholine levels within the prefrontal cortex, nucleus accumbens, caudate putamen, and hippocampus in adult rats. In total 3255 rats were analyzed and we found that when compared with the minority of studies (14%) that did not use AChE inhibitors (these studies yielded basal levels between 0.55 and 2.71 nM depending on the brain site) an up to 350-fold increase in baseline values after the application of an inhibitor could be detected. Especially, the derivates neostigmine bromide and physostigmine sulfate seem to produce dramatic effects. Furthermore, concentration-dependent effects after the application of AChE inhibitors could not be established. In the case of neostigmine bromide an inverted concentration (0.1-10 μM)-response relationship was even detected. We conclude that although the presynaptic action of AChE inhibitors is well understood the nonphysiological and concentration-independent augmentation of the acetylcholine system requires the use of a standard protocol in order to produce replicable and comparable results. Our meta-analysis suggests the use of 0.1 μM neostigmine which produces an approximately 10-fold boost of brain baseline levels.

Effect of carbon dioxide pneumoperitoneum on neuromuscular block of cisatracurium in patients undergoing laparoscopic operation

Objective To investigate the effect of carbon dioxide ( CO2 ) pneumoperitoneum on the neuromuscular block of cisatracurium in patients undergoing laparoscopic operation.Methods Sixty ASA Ⅰ or Ⅱ patients,aged 35-60 yr,with body mass index of 18-24 kg/m2,scheduled for elective hysterectomy,were randomly divided into 2 groups ( n =30 each ):pneumoperitoneum group ( group P) and control group ( group C ).Each group was further divided into 2 subgroups according to the use of the antagonist of neuromuscular block ( n =15 each):no neostigmine group ( group P0 or C0 ) and neostigmine group (group P1 or C1 ).Anesthesia was induced with fentanyl,propofol and cisatracurium and maintained with target-controlled infusion of propofol and remifentanil.Tracheal intubation was performed and the patients were mechanically ventilated.Neuromuscular function was monitored by TOF-Watch SX accelerography (Organon Co.,Organon).A train of four (TOF) stimulation of the ulnar nerve was used.When T,returned to 5％ of control height after CO2 pneumoperitoneum was established,cisatracurium 0.05 mg/kg was injected intravenously in group P.When T1 returned to 25％ of control height after the end of operation,neostigmine was injected intravenously in groups P1 andC1.The clinical duration and recovery index were recorded after CO2 pneumoperitoneum was established.Arterial blood samples were obtained immediately before induction,at 30 and 60 min of pneumoperitoneum,and at the end of operation for blood gas analysis.Results The clinical duration and recovery index were significantly longer in group P0 than in group C0,and in group P1 than in group C1 ( P ＜ 0.05).Compared with group C0,the pH value was significantly decreased and PaCO2 was significantly increased at 30 and 60 min of pneumoperitoneum,and at the end of operation in group P0 ( P ＜ 0.05).Compared with group C1,the pH value was significantly decreased and PaCO2 was significantly increased at 30 and 60 min of pneumoperitoneum,and at the end of operation in group P1 ( P ＜ 0.05).Conclusion CO2 pneumoperitoneum can strengthen the neuromuscular block induced by cisatracurium and prolong the recovery time following antangonism by neostigmine administration in patients undergoing laparoscopic operation. Key words: Atracurium; Carbon dioxide; Pneumoperitoneum; Neuromuscular blockade

Isobolographic Method and Invertebrate (Planarian) Model for Evaluating Combinations of Waterways Pollutants

Agricultural, pharmaceutical, and other biologically active substances are emptied or leach into waterways and groundwater, where they can dose-relatedly cause pharmacologic or toxic effects on the resident or dependent animal species. Standard methods can be used to evaluate the effects of individual substances, but evaluation of combinations of substances is more difficult. The mathematically rigorous method of isobolographic analysis was coupled with a simple in vivo invertebrate model. Planarians were selected because they are the lowest extant species with a centralized nervous system. Neostigmine bromide and monopotassium phosphate (KH2PO4) were selected as representative of two types of potential pollutants. Neostigmine bromide and KH2PO4 individually produced dose-related lethality over a 60-minute observation period with LD50 values of 122 and 70 mM, respectively. The LD50 value of a 1:1 combination of the two was significantly different (p < 0.05) from the isobolographic line of additivity. We used planarians as a representative fresh-water species and joint-action (‘isobolographic’) analysis to examine possible interaction between pollutants. In the demonstrative example reported here, there was a subadditive interaction between a 1:1 fixed-ratio combination of neostigmine bromide (as a representative acetylcholinesterase inhibitor used in pesticides) and potassium phosphate (used in fertilizers and detergents).

Risk factors for airway management after tracheal extubation in old patients

Objective To investigate the risk factors for airway management after tracheal extubation in old patients. Methods 280 patients underwent general anesthesia were enrolled in the study. The procedure of anesthesia induction and maintenance were in the routine method. The patients were with tracheal extubation under clinical standards after operation. Dyspnea was recorded after tracheal extubation. They were divided into dyspnea group and general group. Twelve perioperative variables, ten variables in operation and six post-operative variables of two groups were compared respectively. Results The incidence of dyspnea after tracheal extubation was 8.6％. Analysis identified that obesity( BMI ≥25kg/m2 ), preoperative lung disease and without postoperative neostigmine were the significant risk factors for dyspnea. Conclusion BMI≥25kg/m2 ,preoperative lung disease and without antagonist muscular relaxant were the main risk factors for dyspnea after tracheal extubation in old patients. Key words: Tracheal extubation; Dyspnea; Risk factors; Aged

Update on reversal of postoperative residual nondepolarizing neuromuscular blockade

Background Currently, non-depolarizing neuromuscular relaxant have been widely used in anesthesia for many surgical procedures. After administrating the relaxant, postoperative residual neuromuscular blockage (RNMB) ensues inevitably and mainly results in adverse respiratory events or even death occasionally. Objective Adequate reversal of neuromuscular blockage is crucial to decrease the incidence of postoperative RNMB and contribute to reduce the related complications. Content This article is aimed to review the updates on optimal neuromuscular management strategies, including the necessity of postoperative anticholinesterase agents, the most appropriate reversal opportunity and dose, as well as the new mode of selective reversal of RNMB.Trend The selective reversal of RNMB will reduce the occurrence of postoperative RNMB dramatically, and possibly even avoid RNMB. The novel preventing mode will lead the mainstream of preventing postoperative RNMB. Key words: Non-depolarizing neuromuscular blocking agents; Postoperative residual neuromuscular blockage; Reversal; Neostigmine; Sugammadex

Effect of indwelling catheter after abdominal total hysterectomy by neostigmine injection in the acupuncture point of san yin chiao

Objective To investigate the duration of indwelling catheter and prevention of urinary retention in patients who used PCEA after abdominal total hysterectomy through neostigmine injecting in the acupuncture point of san yin chiao associated with thermo massage on vesical area. Methods 200 patients who used PCEA after abdominal total hysterectomy were randomly divided into the experimental group and the control group, each group had 100 cases. Patients in experimental group received neostigmine injecting in the acupuncture point of san yin chiao associated with thermo massage on vesical area, patients in control group received vitamin C injecting in the acupuncture point of san yin chiao associated with thermo massage on vesical area, and removed the catheter after intervention. The time to voluntary micturition was observed, the residual urine volume was measured, prevention of urinary retention and the side effect were explored. Results The time to voluntary micturition in experimental group was shorter than in control group, there was statistically significant difference( x2 =43.8,P ＜ 0. 01 ); the effective rate of urinary retention prevention in experimental group was 98%, and it was better than in control group which was 61%. There was statistically significant difference( x2 = 41.7 ,P ＜0. 01 ). No bradycardia case, no respiration inhibition case and no hypotension case in the two groups.Conclusions Necstigmine injecting in the acupuncture point of san yin chiao associated with thermo massage on vesical area can shorten the duration of indwelling catheter in patients who used PCEA after abdominal total hysterectomy and it can prevent the incidence of urinary retention. Key words: Hysterectomy; Analgesia, epidural; Urinary Retention; Neostigmine; Nursing; Acupuncture point injection

Neostigmine and FESS

Neostigmine and FESS

Comparative study of 2-hydroxy propyl beta cyclodextrin and calixarene as ionophores in potentiometric ion-selective electrodes for neostigmine bromide

Three novel neostigmine bromide (NEO) selective electrodes were investigated with 2-nitrophenyl octyl ether as a plasticiser in a polymeric matrix of polyvinyl chloride (PVC). Sensor 1 was fabricated using tetrakis(4-chlorophenyl)borate (TpClPB) as an anionic exchanger without incorporation of an ionophore. Sensor 2 used 2-hydroxy propyl β-cyclodextrin as an ionophore while sensor 3 was constructed using 4-sulfocalix-8-arene as an ionophore. Linear responses of NEO within the concentration ranges of 10 −5 to 10 −2, 10 −6 to 10 −2 and 10 −7 to 10 −2 mol L −1 were obtained using sensors 1, 2 and 3, respectively. Nernstian slopes of 51.6 ± 0.8, 52.9 ± 0.6 and 58.6 ± 0.4 mV/decade over the pH range of 4–9 were observed. The selectivity coefficients of the developed sensors indicated excellent selectivity for NEO. The utility of 2-hydroxy propyl β-cyclodextrin and 4-sulfocalix[8]arene as ionophores had a significant influence on increasing the membrane sensitivity and selectivity of sensors 2 and 3 compared to sensor 1. The proposed sensors displayed useful analytical characteristics for the determination of NEO in bulk powder, different pharmaceutical formulations, and biological fluids (plasma and cerebrospinal fluid (CSF)) and in the presence of its degradation product (3-hydroxyphenyltrimethyl ammonium bromide) and thus could be used for stability-indicating methods.

The application of enzyme inhibition to the estimation of small quantities of drugs possessing anticholinesterase activity; the assay of injection of neostigmine methylsulphate.

The application of enzyme inhibition to the estimation of small quantities of drugs possessing anticholinesterase activity; the assay of injection of neostigmine methylsulphate.

Application of the WATR technique for water suppression in 1H NMR spectroscopy in determination of the kinetics of hydrolysis of neostigmine bromide in aqueous solution.

Both ammonium chloride and guanidinium chloride were used to secure water suppression in 1H NMR spectra using the 'Water Attenuation by T2 Relaxation' (WATR) technique. The effect of phosphate buffer in the suppression was investigated over a range of pH values at 80 MHz. The spin-spin relaxation time of water protons at 80 MHz was found to reach a minimum at pH 7.3 in the presence of 0.1 M phosphate buffer and 1 M guanidinium chloride; these conditions were therefore chosen for subsequent use of the WATR technique in a study of the kinetics of hydrolysis of neostigmine bromide. The method was found to be very convenient for studies of the hydrolysis of this representative amide.

Identification of antimicrobial activity among FDA-approved drugs for combating Mycobacterium abscessus and Mycobacterium chelonae

Rapidly growing mycobacteria have long been neglected in drug discovery efforts and this neglect is reflected in the paucity of therapeutic options available for diseases resulting from these infections. The purpose of this work is to identify new candidate drugs for treating non-tuberculous mycobacteria (NTM) by testing FDA-approved drugs for antimicrobial activity against Mycobacterium abscessus and Mycobacterium chelonae, two emerging NTM drug-resistant pathogens. In this study, we screened 1040 FDA-approved drugs against M. abscessus and M. chelonae. Of the drugs screened, 32 compounds exhibited significant antimicrobial activity, with an MIC ≤ 8 mg/L, against M. chelonae, while only 7 compounds showed such activity against M. abscessus. Notably, neostigmine bromide and cinnarizine exhibited highly significant antimicrobial activity against M. chelonae, but had little potency against M. abscessus. Metronidazole and puromycin were the only drugs that acted equipotently against both strains, in decreasing order of effectiveness. The dearth of identified compounds active against M. abscessus exemplifies its ability to resist drugs as well as the resilience of rapidly growing NTM. Repurposing of approved drugs is a viable alternative to de novo drug discovery and development.

Dermal reaction and bigeminal premature ventricular contractions due to neostigmine: a case report

IntroductionNeostigmine is a frequently used acetylcholinesterase inhibitor administered to reverse muscular relaxation caused by nondepolarizing neuromuscular relaxants in patients recovering from general anesthesia. Severe allergic reactions and urticaria are rarely reported following the use of neostigmine bromide, and never with methylsulfate-containing drugs. In this case, bigeminal premature ventricular contractions added to urticaria provides a warning about the possibility of a life-threatening situation.Case presentationWe report the case of a 23-year-old Persian woman who presented with bigeminal premature ventricular contractions along with urticarial lesions on her arm and trunk as soon as she was administered neostigmine methylsulfate after undergoing a laparoscopy for ectopic pregnancy.ConclusionThis case report could be of value not only for anesthesiologists who routinely use neostigmine but also for others who administer the pharmaceutical preparation in other situations. The report presents a rare case of drug reaction following neostigmine use. As a result, one should consider any drug a probable cause of drug reaction. The preparation of resuscitative facilities, therefore, is necessary prior to the prescription of the medication.

Development and Evaluation of Intranasal Mucoadhesiv Microspheres of Neostigmine Bromide

Purpose: Neostigmine bromide, a cholinesterase inhibitor is conventionally given by oral route for the treatment of myasthenia gravis. However, it is very poorly absorbed from gastro-intestinal tract. Intranasal administration is an ideal alternative to the parenteral route for systemic drug delivery. Formulating multiparticulate system with mucoadhesive polymers may provide a significant increase in the nasal residence time. The aim of the present approach was to overcome the drawbacks of the conventional dosage forms of Neostigmine Bromide by formulating intranasal microspheres with Carbopol 974P NF and HPMC K15 M along with film forming polymer ethyl cellulose. Methods: The microspheres were prepared by emulsion solvent evaporation method. The prepared microspheres were characterized for encapsulation efficiency, drug loading, particle size, and surface morphology, degree of swelling, in-vitro mucoadhesion, drug release, in-vivo studies and stability studies. Results: Formulations IN 1 and IN 5 displayed the best results for Carbopol and HPMC based microspheres respectively. Entrapment efficiency was 75.74±0.50% and 70.27±0.61%; mucoadhesion was 98.5% and 85.3%; and drug release up to 8 h was 87.86% and 84.5% for IN 1 and IN 5 respectively. In-vivo studies revealed that the formulations IN 1 and IN 5 showed good bioavailability compared to oral drug administration. Conclusion: Both in-vitro and in-vivo studies conclude that Carbopol based microspheres are better than HPMC based microspheres for the delivery of Neostigmine Bromide.