Cholinergic Drugs PDF

Cholinergic Drugs G4 Azucenas, Bolonias, Cuizon, Fernandez, Larisma, Lobaton, Padin Outline: Review of Autonomic & Somatic NS Cholinergic Receptors Nicotinic Drugs Muscarinic Drugs Inhibitor of Acetylcholine Release Inhibitor of Acetylcholinesterase  Peripheral NS Soma...

Cholinergic Drugs G4 Azucenas, Bolonias, Cuizon, Fernandez, Larisma, Lobaton, Padin Outline: Review of Autonomic & Somatic NS Cholinergic Receptors Nicotinic Drugs Muscarinic Drugs Inhibitor of Acetylcholine Release Inhibitor of Acetylcholinesterase  Peripheral NS Somatic Autonomic Sympathetic Parasympathetic M1 M1 CNS CNS CNS Preganglionic Neuron Preganglionic Neuron Skeletal muscle N2 N2 N1 Ganglion Ganglion Neuromuscular junction Preganglionic Neuron Preganglionic Neuron M1, 2, 3 Effector Cardiac Effector cell Smooth muscle cell Gland ACh Mechanism Cholinergic Receptors - receptors to which acetylcholine binds - perform major roles in neural transmission within the somatic and autonomic nervous systems - due to the diffuse presence of cholinergic receptors, drugs can yield no selectivity Cholinergic Receptors Types of Cholinergic Receptors: 1. Muscarinic Acetylcholine Receptors (mAChRs) 2. Nicotinic Acetylcholine Receptors (nAChRs) Subtypes: 1. mAChRs - M1, M2, M3 2. nAChRs - N1, N2 Muscarinic Receptors - present in CNS and parasympathetic division of ANS - mediates innervation to visceral organs - G-protein coupled receptors - named after muscarine Receptor Subtypes M1 M2 M3 CNS Heart Exocrine glands Brain (cortex, Smooth muscle Smooth muscle hippocampus) Hindbrain Location Exocrine glands (gastric, salivary glands) Sympathetic ganglia Nicotinic Receptors - present in CNS, neuromuscular junction, and autonomic ganglia - voluntary movement and mediate ANS - ligand-gated ion channels - named after nicotine Location  NICOTINIC Cholinergic MUSCARINIC Cholinergic Drugs - mimic ACh (ACh-like effect) - also called parasympathomimetic Anticholinergic Drugs - blocks ACh (atropine-like effect) - also called parasympatholytic Nicotinic Drugs Outline: 1. N1 2. N2 - N1 Agonists - N2 Agonists - N1 Antagonists - N2 Antagonists Nicotine Origin: Tobacco Plant (Nicotiana tabacum) from Solanaceae family Natural occurring chemical compound, belongs to a class of alkaloids. Common in tobacco products, responsible for their addictive properties  (Nm) N1 Neuromuscular Agonists Nicotine Category Details Generic Nicotine Family Cholinergic Nicotinic Agonist Action Binding & activates nicotinic acetylcholine receptors (nAChRs) Indications Smoking cessation for individuals addicted to nicotine. Effects Increased alertness, attention, and memory. mood elevation, heart rate and blood pressure. Gastric motility and secretion. Contraindications Hypersensitivity to nicotine, Pregnancy and breastfeeding, Risk of nicotine toxicity and dependence. Anectine® Category Details Generic Succinylcholine Chloride Family Cholinergic Nicotinic Agonist Action Mimics acetylcholine Indications Muscle relaxation needed for surgical or diagnostic procedures, endotracheal intubation Effects Skeletal muscle relaxant Dose and Dogs: 0.07 mg/kg IV (Morgan 1988) Administration Cats: 0.06 mg/kg IV (Morgan 1988) Contraindications Severe liver disease, suffered traumatic wounds or burns, preexisting hyperkalemia or electrolyte imbalances.  (Nm) N1 Neuromuscular Antagonists Pavulon® Category Details Generic Pancuronium Bromide Family Cholinergic Nicotinic Antagonist Action Binds with receptor Indications Muscle relaxation during surgical procedures or mechanical ventilation and to facilitate endotracheal intubation. Effects Skeletal muscle relaxant Pavulon® Category Details Dose and Dogs: 0.05–0.1 mg/kg IV (Mandsager 1988) Administration Cats: 0.044–0.11 mg/kg IV (Mandsager 1988) Contraindications Hypersensitive, renal dysfunction. Adverse Effects Slight elevations in cardiac rate & blood pressure, hypersalivation Zemuron® Category Details Generic Rocuronium Bromide Family Cholinergic Nicotinic Antagonist Action Compete for cholinergic receptors at the motor end plate. Indications Muscle relaxation during surgical procedures Effects Skeletal muscle relaxant Dose and Dogs: 0.5 mg/kg IV (Alderson et al. 2007) Administration Cats: 0.6 mg/kg IV (Auer & Mosing 2006) Contraindications Hypersensitive patient to rocuronium. Norcuron® Category Details Generic Vecuronium Bromide Family Cholinergic Nicotinic Antagonist Action Compete for cholinergic receptors at the motor end plate. Indications muscle relaxation during surgical procedures or mechanical ventilation and to facilitate endotracheal intubation. Effects Skeletal muscle relaxant Dose and Dogs: 0.01- 0.02 mg/kg IV (Morgan 2003) Administration Cats: 0.02–0.04 mg/kg IV (Morgan 2003) Contraindications Hypersensitive patients, renal dysfunction N2 (Nn) Agonist Drugs Varenicline Category Details Generic Chantix®, Tyrvana® Family Cholinergic Nicotinic Agonist Action Stimulates the receptor weakly, providing some dopamine release to reduce withdrawal symptoms, while blocking nicotine's binding, preventing its reinforcing effects. Indication Smoking cessation therapy Veterinary use: controlling unwanted behaviors linked to compulsive disorders in animals. Contraindication Hypersensitivity, Severe renal impairment, caution in patients with cardiovascular disease Varenicline Category Details Effect Reduced nicotine cravings, Alleviation of withdrawal symptoms, Decreased pleasure derived from smoking. Side Effects Nausea, headache, insomnia, abnormal dreams Dose and Days 1–3: 0.5 mg once daily. Administration Days 4–7: 0.5 mg twice daily. Day 8 onward (up to 12 weeks): 1 mg twice daily. - Oral Administration N2 (Nn) Antagonist Drugs Trimethaphan Category Details Generic Trimethaphan camsylate Family Cholinergic Nicotinic Antagonist (Ganglionic blockers) Action It inhibits transmission in both sympathetic and parasympathetic ganglia Indication Management of hypertensive emergencies in animals (e.g., secondary to conditions like pheochromocytoma). Controlled hypotension during surgical procedures Contraindication Severe hypotension, hypersensitivity, pregnancy Trimethaphan Category Details Effect Rapid reduction in blood pressure for emergency situations. Facilitates controlled hypotension to reduce bleeding during surgery Side Effects Hypotension, tachycardia (reflex), dry mouth, mydriasis (dilated pupils). Gastrointestinal stasis or slow motility, especially in animals with pre-existing GI conditions. Dose and Dogs and cats: Initial dose typically around 0.1–0.3 mg/kg IV Administration bolus, followed by infusion rates adjusted based on response (e.g., 0.05–0.2 mg/kg/min). - IV administration Mecamylamine Category Details Generic Mecamylamine hydrochloride Family Cholinergic Nicotinic Antagonist (Ganglionic blockers) Action It inhibits transmission in both sympathetic and parasympathetic ganglia Indication For the treatment of moderately severe to severe essential hypertension and in uncomplicated cases of malignant hypertension Contraindicati Severe hypotension, renal/hepatic dysfunction on Mecamylamine Category Details Effect Reduction of blood pressure in cases of hypertensive crisis or during surgery. Can help manage sympathetic overactivity (e.g., in cases of excessive catecholamine release). Side Effects Hypotension, bradycardia, tachycardia (reflex), dry mucous membranes, mydriasis (dilated pupils). Dose and Dogs and cats: Initial dose typically around 0.1–0.3 mg/kg IV Administration bolus, followed by infusion rates adjusted based on response (e.g., 0.05–0.2 mg/kg/min). - Administered intravenously or orally Hexamethonium Category Details Generic Hexamethonium bromide Family Cholinergic Nicotinic Antagonist (Ganglionic blockers) Action It inhibits transmission in both sympathetic and parasympathetic ganglia Indication Hypertensive emergencies (rarely used in veterinary practice) Controlled hypotension during surgery Contraindication Hypersensitivity, Severe hepatic or renal dysfunction, Severe cardiovascular diseases Hexamethonium Category Details Effect Reduction of blood pressure in cases of hypertensive crisis. Induces controlled hypotension during surgeries. Side Effects Hypotension, tachycardia (reflex), dry mouth, mydriasis (dilated pupils), urinary retention, constipation. Dose and Hypertensive crisis or controlled hypotension: Initial dose is Administration typically 0.25–0.5 mg/kg IV, with doses adjusted based on the response and clinical condition. - Administered intravenously Summary Receptors Agonist Effect Antagonist Effect N1 (Nm) -Nicotine - Increased - Pancuronium alertness, -Skeletal attention, and - Rocuronium muscle relaxant memory. - Vecuronium -Succinylcholine -Mimics ACh N2 -Trimethaphan - Reduction of (Nn) - Varenicline - Reduced blood pressure nicotine cravings - Mecamylamine - Hexamethonium  Muscarinic Drugs Outline: 1. M1 (Neural) 2. M2 (Cardiac) 2. M3 (Cardiac) - M1 Agonists - M2 Agonists - M3 Agonists - M1 Antagonists - M2 Antagonists - M3 Antagonists  Amanita muscaria Muscarinic Drugs Outline: M1 drugs M2 drugs M3 drugs Agonist: Agonist: Agonist: -Xanomeline -Bethanechol -Pilocarpine -Cevimeline -Carbachol -Arecoline Antagonist: Antagonist: Antagonist: -Perinzepine -Atropine -Ipratropium & Tiotropium -Scopolamine -glycopyrrolate -Hyoscyamine -Benztropine -Oxybutynin -Trihexyphenydil  (Neural) M1 Agonist Drugs Muscarinic Receptor Agonist M1 Agonist Effect: M1 agonists stimulate cognitive functions in the brain and increase gastric acid secretion. Example: Xanomeline, an M1 agonist, is being explored for cognitive enhancement in Alzheimer’s and schizophrenia, potentially improving memory and attention. Xanomeline Category Details Family Alkaloid muscarine Classification Muscarinic Agonist Action Modulates neurotransmitter circuits including acetylcholine, dopamine, and glutamate Indication Treatment of schizophrenia in adults, potential benefits in alzheimer’s disease and other cognitive disorder Contraindication History of hypersensitivity to xanomeline, patients with moderate or severe hepatic impairment, patients with untreated narrow-angle glaucoma, urinary or Gastric retention Xanomeline Category Details Side Effects Nausea, dyspepsia, constipation, vomiting and hypertension, risk of urinary retention particularly in geriatric patients or those with bladder outlet obstruction Dose & Experimental only: doses have not been standardized Administration for animals and require veterinary oversight and specific research protocols Veterinary Use No approved veterinary applications as of now Cevimeline- Origin: Synthetic Compound Category Details Family alkaloid muscarine Classification Selective M1 and M3 agonist Action modulates neurotransmitter circuits including acetylcholine, dopamine, and glutamate Indication Human: Xerostomia associated with Sjögren’s syndrome Veterinary: rarely used directly in animals but can theoretically treat xerostomia in veterinary settings. Contraindication Asthma, bradycardia, arrythmias, peptic ulcers, Gastrointestinal obstructins, severe liver or kidney disease, pregnant/ lactating pets. Arecoline Category Details Origin - Natural alkaoid from Areca catechu (betel nut) Family - Muscarinic Antagonist Action - CNS stimulant with effects on muscarinic M1 receptors Indication Veterinary Use: historical used as an anthelmintic (deworming agent) in livestock. Side effects Vomiting, salivation, diarrhea, and toxicity at high doses. Dose & Dogs & Ruminants: Oral Administration  (Neural) M1 Antagonist Drugs M1 Antagonist Effect: M1 antagonists reduce gastric acid secretion and may have effects on cognition. Example: Pirenzepine is an M1 antagonist that reduces stomach acid secretion, though it’s less commonly used today. Pirenzepine Family - Muscarinic Antagonist Action - Selectively blocks M1 receptors in the stomach Effects - reduces gastric acid secretion Indication - Peptic Ulcer Disease, Gastritis, Gastroesophageal Reflux Disease (GERD) Contraindication - Glaucoma, Urinary retention and hypersensitivity Side effect - Dry mouth, blurred vision, dizziness, Tachycardia, urinary retention, constipation, Confusion and severe allergic reaction Dose & Dogs: Oral Administration Muscarinic Receptor Antagonist Common Alternatives 1. Telenzepine – Another selective M1 antagonist, primarily studied for its effects on the gastrointestinal system and has some similar uses to pirenzepine. 2. Atropine– A non-selective muscarinic antagonist that blocks all muscarinic receptors (M1, M2, M3, M4, M5), but it's less specific and often used in other settings, such as to treat bradycardia or as a pre-anesthetic.. Scopolamine Origin - Natural occurring alkaloid derived from plants of “Solanacae” family (e.g., Atropa belladonna, Hyoscyamus niger) Family - Anticholinergic muscarinic antagonist Action - blocks muscarinic acetylcholine receptors,including receptors in the brain. Effects - Inhibits the action of acetylcholine Indication - Motion sickness (most common use) - Nausea and vomiting post-surgery - Palliative treatment for Ends-of-life symptoms Scopolamine Contraindication - Glaucoma - Tachycardia,myasthenia gravis - Prostatic hypertrophy Side effects - Dry mouth,blurred vision,constipation,urinary retention - Confusion,hallucinations - Tachycardia Dose & - Dogs,cats and horses: SC, IM, IV or transdermal patches Administration Benztropine: Origin-Synthetic compound Classification - Anticholinergic, muscarinic antagonist. Action - Selectively blocks M1 receptors in the stomach Effects - reduces gastric acid secretion Indication - Parkinson’s disease, Drug-induced extrapyramidal symptoms Contraindication - Glaucoma, Bowel or urinary obstruction and Prostatic hypertrophy Side effect - Dry mouth, blurred vision, Tachycardia, urinary retention, constipation Dose & - Dogs and cats: Oral, IM, IV Administration  Trihexyphenidyl: Origin-Synthetic compound Classification - Anticholinergic, muscarinic receptor antagonist. Action - Inhibits M1 muscarinic receptors in the brain (basal ganglia) Effects - reduce symptoms of Parkinsonism. Indication - Parkinson’s disease Contraindication - Glaucoma, Bowel or urinary obstruction,Myasthenia gravis Side effect - Dry mouth, blurred vision, - Tachycardia,urinary retention, constipation - Cognitive dysfuntion,confusion  (Cardiac) M2 Agonist Drugs Muscarinic Receptor Agonist M2 Agonist Effect: M2 muscarinic receptors involved in heart rate regulation, smooth muscle contraction, and glandular secretions Example: Bethanechol and Carbachol Muscarinic Receptor Agonist Bethanechol: Synthetic drug designed to mimic the effects of acetylcholine Muscarinic Receptor Agonist Carbachol : Synthetic drug designed to mimic the effects of acetylcholine Resistant to enzymic degredation  Muscarinic Receptor Agonist Bethanechol Family - Cholinergic Muscarinic Agonist Action - mimics the action of acetylcholine Indication - used primarily to stimulate bladder contractions in small animals Effect - Increase bladder contraction - Promote urination Side effect - Bradycardia (slow heart rate) - Urinary urgency Muscarinic Receptor Agonist Bethanechol Dose of action - For dogs 2.5–25 mg (total dose) PO three times daily (Coates 2004) - For cats 1.25–7.5 mg (total dose) PO two to three times daily (Lane 2003)  Muscarinic Receptor Agonist Carbachol Family - Cholinergic Muscarinic Agonist Action - mimics the effects of acetylcholine but is more stable Indication - Occasionally used for GI atony or bladder issues Effect - Increase peristalsis. - Promotes bladder contraction Side effect - Abdominal cramps - Urinary urgency. - Bradycardia Muscarinic Receptor Agonist Carbachol Contraindication - obstructive diseases - cardiac instability. Dose of Adminitration Opthalmic use ( Dogs and Cats ) - 0.1–0.2 mg/kg (administered SC or IM). - 0.01 - 0.03% solution per eye  (Cardiac) M2 Antagonist Drugs Muscarinic Receptor Antagonist derived from plants in the Solanaceae family plants naturally produce atropine and other related alkaloids : -Atropa belladonna (deadly nightshade), - Datura stramonium ( jimsonweed) - Hyoscyamus niger (henbane). Muscarinic Receptor Antagonist M2 Antagonist Effect: Bind to M2 receptors, preventing acetylcholine from activating these receptors. Increase heart rate by blocking parasympathetic signals to the heart. Example: Atropine and Glycopyrrolate Muscarinic Receptor Antagonist Atropa belladonna Datura stramonium Hyoscyamus niger (deadly nightshade) ( jimsonweed (henbane). Muscarinic Receptor Antagonist Atropine Family - Cholinergic muscarinic Antagonist Action - blocks M2 receptors in the heart - Increase heart rate Indication - used to treat bradycardia (slow heart rate) Effect - Increases heart rate (tachycardia). - Blocks vagal stimulation, useful in bradycardia. Side effect - Dry mouth - blurred vision - Tachycardia - urinary retention Muscarinic Receptor Antagonist Atropine Contraindication - Tachycardias - Myocardial ischemia Dose of - For dogs - during cardiopulmonary cerebral Administration resuscitation (CPCR - efforts: 0.04 mg/kg IV or IO; can repeat every 3–5 minutes for a maximum of 3 doses. - For cats - efforts: 0.04 mg/kg IV or IO; can repeat every 3–5 minutes for a maximum of 3 doses. Muscarinic Receptor Antagonist Glycopyrrolate Family - Cholinergic muscarinic Antagonist Action - blocks M2 receptors in the heart - Increase heart rate Indication - Prevent or treat vagally mediated during anesthesia bradycardia (slow heart rate) Effect - Increase heart rate Side effect - Tachycardia Muscarinic Receptor Antagonist Glycopyrrolate Contraindication - Decrease GI motilty - Prolong retention of the causative agent - Dose of - DOGS: Administration - As an adjunct to anesthesia: - a) 0.011 mg/kg IV, IM, or SC (Package Insert; Robinul®-V —Fort Dodge) CATS: - As an adjunct to anesthesia: a) 0.011 mg/kg IM, for maximum effect give 15 minutes prior to anesthetic administration (Package Insert; Robinul®-V—Fort Dodge)  (Glandular) M3 Agonist Drugs Muscarinic Receptor Agonist M3 Agonist Effect: M3 agonists stimulate smooth muscle contraction and increase secretions, helpful for conditions like dry mouth. Example: Pilocarpine, an M3 agonist, is used to treat dry mouth (xerostomia) and increase tear production in Sjögren's syndrome. Muscarinic Receptor Agonist Pilocarpine: Is a natural alkalosis derived from the leaves of the Pilocarpus plant Used primarily in opthalmology and for certain medical conditions Origin: Derived from Pilocarpine plants, particularly Pilocarpine microphyllus  Muscarinic Receptor Agonist Pilocarpine Origin - Pilocarpus microphyllus Classification - Muscarinic Agonist Action - Stimulates muscarinic acetylcholine receptors,leading to increased secretion of exercise glands (Salivary and Sweat) Effects - contraction of smooth muscle (Eye) Indication - Treatment of glaucoma in cats and dogs, treatment of dry mouth (xerostomia) due to conditions such as Sjögren’s syndrome Dose & Ocular Use: 1-2 drops in affected eyes every 4-6 hours depends on its Administration severity (directly into the conjuctival sac). Xerostomia: 0.1-0.2.g/kg (12h): Oral Muscarinic Receptor Agonist Pilocarpine Contraindication Ocular: patients with retinal deattachment or other ocular conditions where mitosis is contraindicated, and patients with hypersensitive to pilocarpine Systemic: asthma or other respiratory conditions that may be extracted by bronchoconstriction. Side effects: Ocular: - blurred vision,difficulty seeing in lowlight due to miosis, Eye discomfort/irritation and headache Systemic: -sweating,flushing and increased salivation. Nausea,vomiting,diarrhea and abdominal cramping. Bradycardia and hypotension  (Glandular) M3 Antagonist Drugs Muscarinic Receptor Antagonist M3 Antagonist Effect: Selectively block M3 muscarinic receptors Relax smooth muscle and reduce glandular secretions. Example: Ipratropium and Tiotropium Muscarinic Receptor Antagonist Example: Ipratropium and Tiotropium (Bromide) Origin Atropa Belladona (deadly nightshade) Family Muscarinic Antagonist Action Selectively blocks M3 receptors in the airways Effects to produce bronchodilation and reduce mucus secretion. Indication Used to treat asthma, COPD, overactive bladder Side effect Dry mouth, Throat irritation Dose & Dogs & Cats: Inhalation via Nebulizer and Aerosol Administration  Muscarinic Receptor Antagonist Example: Hyoscyamine Origin naturally occurring tropane alkaloid derived from plants in the Solanaceae family, such as Atropa belladonna and Hyoscyamus niger Family Muscarinic Antagonist (anticholinergic) Action It blocks the action of acetylcholine at muscarinic receptors, particularly at the M3 subtype in smooth muscles and glands Effect It reduces parasympathetic nervous system activity, leading to a variety of effects: Smooth muscle relaxation, Reduction of secretions, Decreased peristalsis Indication Irritable Bowel Syndrome (IBS), Gastrointestinal disorders, Bladder spams, Muscarinic Receptor Antagonist Example: Hyoscyamine Dose & -Dogs: Oral-0.1-0.2 mg/kg (8-12h) GI disorders, UT disorder Administration Cats : Oral-0.05-0,1 mg/kg (GI and UT disorder) horses: Oral-0.01-0.05 mg/kg GI disorder Contraindication - Glaucoma, Myasthenia gravis, Tachycardia, Prostatic hypertrophy, Obstructive gastrointestinal conditions, Hypersensitivity Side effects - Dry mouth, Blurred vision, Constipation, Urinary retention, Tachycardia, Dizziness, Nausea,Photophobia, Increased  Muscarinic Receptor Antagonist Example: Oxybutynin Origin - Synthetic drug Family Muscarinic Antagonist (anticholinergic) Action Selectively blocks the action of acetylcholine at muscarinic receptors, particularly in the smooth muscle bladder. Effect - Prevents acetylcholine from binding to the receptors, which results in smooth muscle relaxation (detrusor muscle) - reduces bladder spasms and increases urinary bladder. Indication Overactive bladder syndrome, neurogenic bladder, Bladder spasms. Muscarinic Receptor Antagonist Example: Oxybutynin Dose & -Humans: Administrat Initial dose: 5 mg 1-2 times daily ion Maintenance Dose: 5-10 mg 2-3 times daily Contraindic - Urinary retention, Gastric retention, Glaucoma, ation hypersensitivity and severe ulcerative colitis Side effects - Dry mouth, Blurred vision, Constipation, Urinary retention, Tachycardia, Dizziness, Nausea,Photophobia, Heat intolerance  Inhibitor of Acetylcholine Release Inhibitor of Acetylcholine Release Botulinum Toxin (Botox): produced by Clostridium botulinum bacteria blocks acetylcholine by cleaving proteins resulting in temporary flaccid paralysis of the targeted muscles. This effect typically lasts 3-6 months. Toxic Effects (Botulism): Foodborne or wound botulism causes muscle paralysis, respiratory failure, and can be life-threatening if untreated. USES: Inhibitor of Acetylcholine Release Aminoglycosides block the influx of calcium ions into nerve endings reduce release of acetylcholine from vesicles in the presynaptic neuron Without sufficient calcium, acetylcholine release is significantly reduced, leading to a decrease in neurotransmission at the neuromuscular junction. Inhibitor of Acetylcholine Release Diseases Treated: These antibiotics treat bacterial infections, especially gram-negative infections (E. coli, Pseudomonas, etc.). Inhibitor of Acetylcholine Release Side Effects: Neuromuscular Blockade: Muscle weakness or respiratory paralysis (eg. patients with myasthenia gravis) Nephrotoxicity and Ototoxicity: hearing loss and kidney damage Inhibitor of Acetylcholine Release Magnesium Ions inhibit calcium entry at nerve terminals, which is necessary for vesicle fusion and ACh release. used clinically to manage preeclampsia and other conditions involving neuromuscular blockade. Inhibitor of Acetylcholine Release Diseases Treated Preeclampsia and Eclampsia: Used as magnesium sulfate to prevent seizures in pregnant women. Side Effects Neuromuscular Blockade: causing muscle weakness or even respiratory paralysis, particularly in people with kidney issues or myasthenia gravis. Inhibitor of Acetylcholine Release Vesamicol inhibits the vesicular acetylcholine transporter (VAChT) prevents the uptake of acetylcholine into synaptic vesicles, reducing its availability for release Inhibitor of Acetylcholine Release Uses: Investigational use in research to study neurotransmitter dynamics. Side Effects: Limited clinical use due to its specificity and potential side effects. Inhibitor of acetylcholinesterase Physostigmine an acetylcholinesterase inhibitor (AChEl), potentiates the response to acetylcholine (ACh) Helps prolong the activity of acetylcholine in the body. Clinical Applications: Myasthenia Gravis - when antibodies block AChr leading to muscle weakness; Physostigmine increase the ACh levels and improve the muscle function. Glaucoma— the Physostigmine is used topically to constrict the pupil and reduce intra ocular pressure NOTES References: Handbook of Veterinary Pharmacology Dukes’ Physiology of Domestic Animals 13th Edition Cholinergic - Definition, Effects and Drugs: https://biologydictionary.net/cholinergic Physiology, Cholinergic Receptors: https://www.ncbi.nlm.nih.gov/books/NBK526134 References: Muscarinic Receptors: https://www.egpat.com/tutorials/cholinergic-agonists/musc arinic-receptors Physiology, Acetylcholine: https://www.ncbi.nlm.nih.gov/books/NBK557825/ Plumb, D. C. (2011). Plumb’s veterinary drug handbook (7th ed.). Wiley-Blackwell.