Chapter 6 Parasympathomimetics Cholinoceptors Agonists Anticholinesterases
Chapter 6 Parasympathomimetics Cholinoceptors Agonists Anticholinesterases
Sectionl. M-R Agonists choline esters:均含有季铵基团,(MR,NR) acetylcholine(ach): unstable, low selectivity methacholine(醋甲胆碱) carbachol(卡巴胆碱) bethanechol chloride(氯贝胆碱) alkaloidS:(M-R) carpine muscarine arecoline(槟榔碱)
Section1. M-R Agonists choline esters: 均含有季铵基团, (M-R, N-R) acetylcholine (Ach)：unstable, low selectivity methacholine (醋甲胆碱) carbachol (卡巴胆碱) bethanechol chloride (氯贝胆碱) alkaloids: (M-R) pilocarpine muscarine arecoline (槟榔碱)
Choline esters Acetylcholine(Ach,乙酰胆碱) PHarmacological actions Directly activate M, N-R .o muscarinic actions: in small dose nicotinic actions: in large dose Effective in large dose iv Local effect by im, sc
[Pharmacological actions] Directly activate M, N-R ❖ muscarinic actions: in small dose ❖ nicotinic actions: in large dose Acetylcholine (Ach,乙酰胆碱) Effective in large dose iv Local effect by im, sc Choline esters
AUTONOMIC SOMATIC Sympathetic innervation Sympathetic Parasympathetic adrenal dulla Ganglionic transmitter Acetylcholine Acetylcholine Acetylcholine no ganglia Nicotinic Nicotinic Nicotinic Adrenal medulla Postganglionic neurons NeuroeffectorEpinephrine released Norepinephrine Acetylcholine Acetylcholine into the blood Adrenerg Adrenergi Muscarinic receptor receptor receptor 多 NicotinIc Effector organs stue横纹肌 FIgure 3.6 Summary of the neurotransmitters released and the types of receptors found within the autonomic and somatic nervous systems. [Note: This schematic diagram does not show that the parasympathetic ganglia are close to or on the surface of the effector organs and that the postganglionic fibers are usually shorter than the preganglionic fibers
横纹肌
Robert Furchgott 1. muscarinic actions (cardiovascular system vessel dilation,BP↓( reflective HRT)HR↓ a. NO release↑ (M3R→EDRF(NO)↑→GC→cGMP↑→ intracellular Ca2) b. NA release .o Heart depression: atrium>ventricles negative(chronotropic, dromotropic, inotropic) effect Direct effect: mainly in atrium Indirect effect (negative feedback NA release D): ventricles
1. muscarinic actions (1) cardiovascular system ❖ vessel dilation, BP↓ (reflective HR↑) HR a. NO release↑ (M3 R →EDRF(NO) ↑→GC →cGMP↑→ intracellular Ca2+↓) b. NA release↓ ❖ Heart depression: atrium>ventricles negative (chronotropic, dromotropic, inotropic) effect Direct effect: mainly in atrium Indirect effect (negative feedback NA release ↓): ventricles Robert Furchgott
mechanism of negative chronotropic effect ↓Ca→ Lautomatic depolarization mechanism of negative dromotropic effect T ERP of Atrioventricular node purkinje fibers i conduction mechanism of negative inotropic effect atrium:↑K+efux>↑ repolarization action potential duration l, ERPV, Ca2+v ventricles: presynaptic membrane M-R NA release
mechanism of negative chronotropic effect ↓Ca2+ →↓automatic depolarization mechanism of negative dromotropic effect ↑ ERP of Atrioventricular node & Purkinje fibers →↓conduction mechanism of negative inotropic effect atrium: ↑ K+ efflux→ ↑ repolarization → action potential duration ↓ , ERP↓，Ca2+ ventricles: presynaptic membrane M-R →NA release↓
(2) splanchnic smooth muscle O gastrointestinal tract: excitation ,s motility increase; secretion stimulation ② urinary bladder: detrusor(逼尿肌) contraction 令 trigone(三角区) sphincter relaxation ③ bronchus: contraction
(2) splanchnic smooth muscle ① gastrointestinal tract: excitation ❖ motility increase; secretion stimulation ② urinary bladder: ❖ detrusor (逼尿肌) contraction ❖ trigone (三角区) sphincter relaxation ③ bronchus: contraction
3)others O glands secretion: increasingly 2) eyes miosis (iris sphincter contraction near vision(ciliary muscle contraction)
(3) others ① glands secretion: increasingly ② eyes: miosis (iris sphincter contraction ) near vision (ciliary muscle contraction)
Organ Response M,M y Sphincter muscle of iris Contraction(miosis) Ciliary muscle Contraction for near vision Heart Sinoatrial node Decrease in rate (negative chronotropy) Atria Decrease in contractile strength (negative inotropy) Decrease in refractory period 不应期 Atrioventricular node Decrease in conduction velocity(negative dro- motropy) Increase in refractory period Ventricles Small decrease in contractile strength Blood vessels Arteries Dilation (via EDRF. Constriction (high-dose direct effect Dilation (via EDRF. Constriction(high-dose direct effect Lung Bronchial muscle Contraction (bronchoconstriction) Bronchial glands I Stimulation Gastrointestinal tract Motility Increase Sphincters Relaxation Secretion Stimulation Urinary bladder Detrusor Contraction Trigone and sphincter Relaxation Glands Sweat, salivary lacrimal Secreti。n 鼻咽部的 nasopharyngeal
不应期 鼻咽部的 M1 M2 M3 M1M3
2. nicotinic actions (ganglion, skeletal muscle, adrenal medulla NH-R: co-innervation and dominant theory adrenaline release N-R: skeletal muscle contraction
2. nicotinic actions (ganglion, skeletal muscle, adrenal medulla) ❖ NN -R: co-innervation and dominant theory adrenaline release ❖ NM -R: skeletal muscle contraction