Drug intervention-- Cholinergic transmission (Rate-limiting) Precursor transport ...........Hemicholiniums ↓：Stimulatory Synthesis ⊥：Inhibitory Cholinergic antagonists Solid:Agonistic 0 Dotted:Antagonistic Atropine (anti-M) hexamethonium Storage Vesamicol (anti-NM) Trimetaphan 0 (anti-NN) Release Botulinum toxin Cholinergic agonists (direct acting) AntiChE Carbachol Ach Oxotremorine Reversible (neostigmine) Irreversible (organo- phosphate) Receptor Degradation +action by AchE Definition of Agonist and Antagonist: Agonist:(1)A natural ligand that activates a receptor.(2)A drug that has properties similar to a natural ligand in activating the same receptor. Antagonist:(1)A receptor-specific blocker.(2)A molecule,such as a drug(e.g.. enzyme inhibitor)or a physiologic agent(e.g.,hormone),that diminishes or prevents the action of another molecule. Mode of Action: Direct-acting: Molecule that physically binds to the target for its effect. Example:carbachol activates cholinergic receptors. Indirect-acting:Molecule that exerts effect on the target by interacting with another molecule. Example:neostigmine blocks AchE,causing Ach accumulation. Mode of action and agonism are different concepts.For example,a direct- acting molecule can be either agonistic or antagonistic. 99 Drug intervention -- Cholinergic transmission Precursor transport Synthesis Hemicholiniums Storage Vesamicol Release Botulinum toxin Degradation by AchE Receptor + action Ach Cholinergic agonists (direct acting) Carbachol Oxotremorine (Rate-limiting) AntiChE Reversible (neostigmine) Irreversible (organo￾phosphate) ↓ : Stimulatory ⊥ : Inhibitory Solid: Agonistic Dotted: Antagonistic Cholinergic antagonists Atropine (anti-M) hexamethonium (anti-NM) Trimetaphan (anti-NN) Agonist: (1) A natural ligand that activates a receptor. (2) A drug that has properties similar to a natural ligand in activating the same receptor. Antagonist: (1) A receptor-specific blocker. (2) A molecule, such as a drug (e.g., enzyme inhibitor) or a physiologic agent (e.g., hormone), that diminishes or prevents the action of another molecule. Direct-acting: Molecule that physically binds to the target for its effect. Example: carbachol activates cholinergic receptors. Indirect-acting: Molecule that exerts effect on the target by interacting with another molecule. Example:neostigmine blocks AchE, causing Ach accumulation. Definition of Agonist and Antagonist: Mode of Action: Mode of action and agonism are different concepts. For example, a direct￾acting molecule can be either agonistic or antagonistic