parasympa ganglionic

• Carbachol (Carbamoylcholine)

  1. Extremely potent choline ester active at muscarinic and nicotinic receptors

  2. Used for emergency treatment of colic in horses and ruminal stasis in cattle
• Acetylcholine (ACh)

  1. Essential for maintenance of body homeostasis

  2. Not used therapeutically due to acting simultaneously at various tissue sites and having a brief duration of action
• Therapeutic uses of choline esters

  • Methacholine and bethanechol not frequently used in clinical veterinary medicine
  • Methacholine used to control tachycardia of supraventricular origin
  • Bethanechol used to treat urinary bladder atony in cats after urolithiasis
  • Carbachol used in treatment of colic, impactions of the intestinal tract, ruminal atony, and impaction in cattle
• Bethanechol (Carbamoylmethylcholine)

  1. Primarily a muscarinic agonist with little stimulant effects on nicotinic receptors

  2. Used to treat urinary bladder atony in cats and colic in horses
• Cholinergic Drugs Classification

  • Choline Esters
  • Natural Alkaloids
  • Nicotine
  • Acetylcholine
  • Muscarine
  • Lobeline
  • Methacholine
  • Pilocarpine
  • Phenyltrimethylammonium (PTMA)
  • Bethanechol
  • Arecholine
  • Dimethylphenylpiperazinium (DMPP)
  • Irreversible AntiChE agents
  • Reversible AntiChE agents
  • Organophosphates
  • Carbamates
  • Acridine
  • Diiosopropyl fluoro-Carbaryl (Sevin)
  • Neostigmine
  • Tacrine
  • Phosphate, DFP (Dyflos)
  • Propoxur (Baygon)
  • Physostigmine
  • Malathion
  • Parathion
  • Edrophonium
  • Tabun, Sarin, Soman
  • Pyridostigmine
• Methacholine (Acetyl-β-methylcholine)

  1. Synthetic choline ester used occasionally in human therapeutics

  2. Causes muscarinic effects on cardiovascular function similar to ACh, less active on GI system, lacks nicotinic action
• Cholinesterase inhibitors

  • Indirect acting parasympathomimetic agents
  • Inactivate or inhibit AChE and pseudoChE
  • Intensify the activity of endogenous ACh
• Hydrolysis of ACh by AChE

  1. Involves electrostatic attraction of positively charged N+ of ACh to the aromatic pocket and nucleophilic attack by serine –OH activated by adjacent histidine

  2. Leads to acetylation of the serine, producing acetic acid and choline
• Pilocarpine

  • Obtained from the leaves of Brazilian shrubs Pilocarpus jaborandi and P. microphyllus
  • Prominent muscarinic actions
  • Stimulates ganglia mainly through ganglionic muscarinic receptors
  • Effective in stimulating flow of secretions from exocrine glands
  • Causes contraction of GI smooth muscle
  • Has a potent constrictor effect on the pupil
• Arecholine

  • Found in the beetle nut, the seed of the beetle palm (Areca catechu)
  • Muscarinic and nicotinic actions
  • Stimulates secretion of the glands of the digestive tract
  • Increases peristaltic movement of the gut
  • Contracts the urinary bladder
• Muscarine

  • Found in the poisonous mushrooms Amanita muscaria
  • Has only muscarinic actions
  • Not used therapeutically, but is of toxicological importance
• Reversible inhibitors

  • Edrophonium and tacrine attach only to the anionic site of the enzyme
  • Physostigmine and neostigmine bind to both active sites
• Carbachol has been used in the treatment of colic and impactions of the intestinal tract. It is also used in the treatment of ruminal atony and impaction in cattle
• Carbachol, Pilocarpine, Arecholine, and Muscarine are natural alkaloids
• Therapeutic uses of cholinomimetic alkaloids

  1. Solutions of 0.5 to 2% of pilocarpine are used for instillation into the conjunctival sac for treatment of glaucoma

  2. Pilocarpine is used as a miotic to counteract mydriatics and prevent or break adhesions of iris with lens or cornea
• Edrophonium and tacrine attach only to the anionic site of the enzyme


  They serve as alternate substrates for AChE
• Treatment of organophosphate poisoning: The first line of treatment consists of administration of atropine to counter muscarinic effects of ACh @ 0.2 to 0.5 mg/kg b.wt. (maximum dose = 1 mg/kg)
• Physostigmine and neostigmine bind to both anionic and esteratic sites of the enzyme

  The carbamylation of the enzyme with neostigmine and physostigmine is of longer duration than the inhibition by edrophonium
• Effects and toxicity of organophosphate poisoning: Organophosphate poisoning produces diffuse cholinomimetic effects including profuse salivation, vomiting, defaecation, hypermotility of the GI tract, urination, bradycardia, hypotension, severe bronchoconstriction, and excess bronchial secretions. These signs reflect excess activation of muscarinic receptors of post-ganglionic parasympathomimetic actions
• Physostigmine is an alkaloid extracted from the dried ripe seeds of a vine, Physostigma venenosum which grows in tropical West Africa. It is also known as Calabar bean or “Ordeal bean”. Physostigmine is used for its ability to constrict the pupil or as miotic and in the treatment of deadly nightshade poisoning
• Comparative features of Physostigmine and Neostigmine

  • Source: Calabar bean, Synthetic
  • Chemistry: Tertiary amine derivative, Quaternary ammonium compound
  • Oral absorption: Good, Poor
  • CNS actions: Present, Absent
  • Applied to eye: Penetrates cornea, Poor penetration
  • Direct action on cholinoceptors: Absent, Present
  • Prominent effect on Autonomic effectors: Skeletal muscle
  • Important use: Miotic (in glaucoma), Myasthenia gravis
  • Dose: 0.5 – 1 mg (man) oral or parenteral, 0.1 – 1% in eye drops, 0.5 – 2.5 mg (man) i.m./ s.c
  • Duration of action: Systemic - 4 to 6 hours, Eye – 6 to 24 hours, 4 to 6 hours
• Mechanism of action of irreversible inhibitors: Organophosphates act as irreversible inhibitors of the cholinesterases in mammals. These compounds irreversibly phosphorylate the esteratic site of both AChE and the non-specific or the pseudocholinesterase throughout the body. Endogenous ACh is not inactivated and the resulting effects are due to the excessive preservation and accumulation of endogenous ACh
• During the period where the enzyme inhibitor complex exists

  The enzyme will not hydrolyze its natural substrate ACh
• Neostigmine is the salt of a synthetically produced substance structurally related to physostigmine. It is used as purgative and in the treatment of atony of urinary bladder
• Tacrine inhibited enzyme does not involve hydrolysis of the inhibitor


  Only its diffusion – so action is brief
• In addition to the muscarinic effects, skeletal muscle fasciculations, twitching, and subsequently muscle paralysis occur due to persistent excessive stimulation of the nicotinic receptors of skeletal neuromuscular junctions, resulting in the depolarizing type of striated muscle paralysis. Convulsions and frequently death are seen in organophosphate poisoning caused by the penetration of the agents into the CNS and subsequent intensification of the activity of ACh at CNS sites
• Anticholinergic drugs classification based on Origin & Structure

  • Tertiary amine Compounds: Atropine, Pirenzepine, Methantheline, Homatropine, Dicyclomine, Propantheline, Methscopolamine bromide, Cyclopentolate, Isopropamide, Ipratropium bromide, Oxyphenecyclimine, Glycopyrrolate, Tiotropium bromide, Tropicamide
  • Quaternary ammonium Compounds: Homatropine methyl bromide
  • Tertiary amine Compounds: Atropine methylnitrite
• Therapeutic use of Irreversible inhibitors

  1. The only drug indication is the relief of glaucoma where a single instillation of dyflos (di-isopropylfluorophosphate) or echothiopate acts for several weeks

  2. Organophosphates and carbamates are used as insecticides for the control of insect vectors and ectoparasites
• Pharmacological actions of Parasympatholytics

  Cardiovascular system: Small doses of atropine cause an initial temporary bradycardia, high doses cause tachycardia. Atropine antagonizes the fall in blood pressure caused by choline esters. 2. GI tract: Smasmolytic effect on GI smooth muscles, block increase in tone and motility of GIT caused by cholinergic drugs. 3. Respiratory tract: Inhibition of bronchial secretions and dilatation of bronchi. 4. Eye: Mydriasis and cycloplegia. 5. Urinary tract: Spasmolytic effect on ureters and urinary retention. 6. Skin: Anhydrotic action in man
• Anticholinergic drugs classification based on Mode of Action

  • Atropine, Scopolamine, Homatropine: M1 Antagonist, M2 Antagonist, M3 Antagonist, M4 Antagonist
  • Pirenzepine, Methoctramine, Hexahydrosiladenifenidol, Himbacine, Telenzepine, Gallamine
• Treatment of organophosphate poisoning

  1. First line: Administration of atropine to counter muscarinic effects of ACh @ 0.2 to 0.5 mg/kg b.wt. (maximum dose = 1 mg/kg). Administered as 0.15% solution of atropine in physiological saline

  2. Second line: Use of oxime reactivators such as diacetyl monoxime (DAM), 2-pyridine aldoxime methiodide (2-PAM or pralidoxime), obidoxime etc. to reactivate the phosphorylated AChE enzyme and accelerate clinical recovery
• Mechanism of action of muscarinic blockers

  Atropine and related drugs block the cholinergic muscarinic receptors by acting as competitive antagonists of ACh or other direct acting cholinergic drugs
• Usefulness of oxime reactivators

  • Limited to a short period (minutes or hours depending on the compound) due to the enzyme phosphate complex becoming resistant when a further group is removed by hydrolysis, known as "ageing"
• Atropine is an alkaloid extracted from the leaves of belladonna plants Atropa belladonna (deadly nightshade), Datura stramonium (Jimson weed) and Hyoscyamus niger (Henbane)
• Riasis is due to blockade of cholinergic influence and dominance of adrenergic effect
• Effects of atropine in relation to dose
• Atropine is a racemic mixture of d-hyoscyamine and l-hyoscyamine. The laevo form of hyoscyamine is biologically active
• Skin

  1. Anhydrotic action in man (cholinergic) and consequently rise in body temperature

  2. Does not prevent sweating in horses (adrenergic)
• Drugs alter the ganglionic function by either stimulating (ganglionic stimulants) or blocking (ganglionic blo
• Alternate use of a mydriatic (e.g. atropine) and a miotic (e.g. physostigmine 0.5%) can be used to prevent adhesions involving the iris