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And Related Agents

Cholinergic drugs thea

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  • And Related Agents

  • Cholinergic Drugs and Related AgentsMimic the action of acetylcholine or,Blocks the action of acetylcholine (ACh)

    *Cholinergc Drugs - stimulates the parasympathetic nervous system (rest and digest).

  • Acetylcholineis one of many neurotransmitters in theautonomic nervous system(ANS)only neurotransmitter used in the motor division of thesomatic nervous system

  • Cholinergic Receptors

    Nicotinic receptors- 2 Subtypes

    Muscarinic receptors- 5 Subtypes

  • Nicotinic Receptorscoupled directly to ion channelsfirst neurotransmitter isolated and purified in an active formIt is a glycoprotein embedded into the polysynaptic membrane that can be obtained from the electric organs of the marine ray, Torpedo californica and the electric eel, Electrophorus electricus. When the neurotransmitter ACh binds to the nicotinic receptor, it causes a change in the permeability of the membrane to allow passage of small cations Ca2, Na, and K. This depolarization results in muscular contraction at a neuromuscular junction or, as occurs in autonomic ganglia, continuation of the nerve impulse.

  • Nicotinic receptor subtypes

    N1N2At the neuromuscular junctionFound in autonomic gangliablocked by succinycholine, d-tubocurarine, and decamethonium and stimulated by phenyltrimethylammonium blocked by hexamethonium and trimethaphan but stimulated by tetramethylammonium and dimethyl 4-phenylpiperazinium

  • Muscarinic Receptorsplay an essential role n regulating the function of organs innervated by the autonomic nervous system to maintain homeostasis.

    Its action can result to stimulation/inhibition of the organ system that is affected.

  • Muscarinic Receptor subtypes

    M-receptors subtypesM1M2M3M4M5Other nameneuralCardiac muscarinic receptorsGlandular muscarinic receptorsLocationExocrine glands and autonomic gangliaAtria and conducting tissue of the heartExocrine glands and smooth muscleCNSSubstantia nigra (cns)FunctionAffects arousal attention, REM, emotional response, affective disorderCardiac inhibitionLacrimal, salivaryMostly stimulatory effectDirect regulatory action on K and Ca ion channelsMay regulate dopamine release at terminals within the striatum

  • Second messenger systemPhosphoinositol System

  • Adenyl Cyclase

  • Ion Channel

  • Cholinergic Neurochemistry

    Cholinergic neurons synthesize, stores and releases ACh .It describes anyneuron which mainly uses theneurotransmitter acetylcholine(ACh) to send its messages. Cholinergicneurons provide the primary source of acetylcholine to thecerebral cortex, and are known for their role in promoting cortical activation during both wakefulness and duringrapid eye movement (REM) sleep.Neurochemistry is the specific study ofneurochemicals includingneurotransmitters and other molecules (such as psychopharmaceuticals) that influence the function ofneurons.

  • CHOLINERGIC AGONISTcholinergic agents; parasympathomimetic; mimics effect of parasympathetic nervous system neuroransmittersA substance (orligand) is cholinergic if it is capable of producing, altering, or releasingacetylcholine("indirect-acting") or mimicking its behaviour at one or more of the body'sacetylcholine receptortypes ("direct-acting").

  • Cholinergic Stereochemistryis the study of thechemistryinvolved in the relative spatial arrangement of cholinergic atomsandmolecules.Has 3 techniques

  • X-ray crystallographyis a method of determining the arrangement ofatomswithin acrystal, in which a beam ofX-raysstrikes a crystal anddiffractsinto many specific directions.

  • Nuclear magnetic resonance

    aphysical phenomenonin whichnucleiin amagnetic fieldabsorb and re-emitelectromagnetic radiation. This energy is at a specificresonancefrequency which depends on the strength of the magnetic field and the magnetic properties of theisotopeof the atoms

  • Molecular Modelling by computation encompasses all theoretical methods and computational techniques used tomodel or mimic the behavior ofmolecules.


    is the relationship between thechemicalor 3D structure of a molecule and itsbiological activity. The analysis of SAR enables the determination of the chemical groups responsible for evoking a target biological effect in the organism.

  • 3 Categories of the Alteration on the MoleculeOnium groupEster functionCholine moeity

  • ProductsOxotremorine[1-(pyrrolidono)-4-pyrrolidino- 2-butyne]CNS muscarinic stimulantStudied to be a drug treatment on Alzheimers disease

  • ArecolineAlkaloid obtain from seed of betel nut (Areca catechu)


    blocks theneurotransmitteracetylcholinein thecentraland theperipheral nervous system.cholinergic blockers, parasympatholytics or anticholinergic

  • Acetylcholine chloride

  • Carbachol

  • Betanechol Chloride, USP


  • Cholinesterase inhibitorsbind to cholinesterase resulting in increased acetylcholine in the synapses, causing increased parasympathetic activityAcetylcholinesterase- an enzyme that rapidly breaks down the neurotransmitter, acetylcholine, so that it does not over-stimulate post-synaptic nerves, muscles, and exocrine glandsAcetylcholinesterase inhibitor - a chemical that binds to the enzyme, cholinesterase, and prevents it from breaking down the neurotransmitter, acetylcholine.

  • 2 types of cholinesterase:

    Acetylcholinesterase (AChE) its inhibition prolongs the duration of the neurotransmitter in the junction and produces pharmacological effects similar to those observed when ACh is administered.

    Butyrylcholinesterase (BuChE) (pseudocholinesterase), is located in human plasma. Has catalytic property similar to AChE


    REVERSIBLE INHIBITORS has therapeutic application

    IRREVERSIBLE INHIBITORS these chemicals are nerve poisons and had been use in warfare, bioterrorism, and as agricultural insecticides. They permit ACh to accumulate at nerve endings and exacerbate ACh-like actions.

  • Physostigmine, USPPhysostigma venemosum.topical application in the treatment of glaucomaantidote for atropine poisoning and other antcholinergic drugs.

  • Neostigmine Bromide - antidote to nondepolarizing neuromuscular blocking drugs treatment of myasthenia gravis.

  • Demecarium bromide, USP long acting miotic use to treat wide angle glaucoma and accommodative esotropia.

  • Donezepil indicated for the treatment of mild-to-moderate Alzheimers disease

  • GalantamineLeucojum aestivum belonging to the Amaryllidaceae family and from the bulbs of the daffodil, Narcissus pseudonarcissus; no effect on butyrylcholinesterase; acts at allosteric nicotinic sites, further enhancing its cholinergic activity.

  • Rivastigmine the FDA approved its use in mild-to-moderate Alzheimers disease in April 2000. In July 2007, it was granted approval for use in managing mild-to-moderate dementia associated with Parkinsons disease.

  • Irrevrsible InhibitorsIsofluorphate, USP(Floropryl) - Stable in peanut oil (1 yr).Solutions in peanut oil can be sterilized by autoclaving; Should be stored in glass containers, discoloration when decomposed;treatment of glaucoma

  • Malathion - Water insoluble phophodithioate esterused as agricultural insecticide; generally, cause poisoning only by ingestion of large doses.

  • Parathion - (Thipos); Decomposed at pH above 7.5; causes poisoning by inhalation or dermal absorption; Used as an agrcultural insecticide

  • Hexaethyltetraphosphate (HETP) and Tetraethylpyrophosphate (TEPP) - Developed by the Germans during WWII; Insecticide against aphids; Fruit trees or vegetables sprayed retain no harmful residue after a period of a few days or weeks, depending on the weather conditions.; Workers spraying with these agents should use extreme caution so that vapors are not breathed and none of the vapor or liquid comes in contact with the eyes or skin.


    Anticholinergic action by drugs and chemicals apparently depends on their ability to reduce the number of free receptors that can interact with Ach. Some theories indicate that the amount of drug-receptor complex formed at a given time depends on the affinity of the drug for the receptor and that a drug that acts as an agonist must also possess another property called efficacy or intrinsic activity.