Distribution of adrenoceptor subtypes type tissue action Most vascular smooth muscle Contraction pupillary dilator muscle Contraction(dilates pupil) al Pilomotor smooth muscle Erects hair Prostate contraction heart Increase force of contraction Postsynaptic CNS adrenoceptors Probably multiple platelet aggregation a2 Adrenergic and cholinergic nerve terminal Inhibition of transmitter release Some vascular smooth muscle contraction Fat cells Inhibition of lipolysis B1 heart Increase force and rate of contraction Respiratory,uterine and vascular smooth muscle Promote smooth muscle relaxation B2 Skeletal muscle Promote potassium uptake Human liver Activates glycogenolysis B3 Fat cells Activates lipolysis D1 Smooth muscle Dilates renal blood vessels D2 Nerve endings Modulates transmitter release
type tissue action α1 Most vascular smooth muscle Contraction pupillary dilator muscle Contraction (dilates pupil) Pilomotor smooth muscle Erects hair Prostate contraction heart Increase force of contraction α2 Postsynaptic CNS adrenoceptors Probably multiple platelet aggregation Adrenergic and cholinergic nerve terminal Inhibition of transmitter release Some vascular smooth muscle contraction Fat cells Inhibition of lipolysis β1 heart Increase force and rate of contraction β2 Respiratory, uterine and vascular smooth muscle Promote smooth muscle relaxation Skeletal muscle Promote potassium uptake Human liver Activates glycogenolysis β3 Fat cells Activates lipolysis D1 Smooth muscle Dilates renal blood vessels D2 Nerve endings Modulates transmitter release Distribution of adrenoceptor subtypes
Drugs Acting on the Sympathetic Nervous System 81 ⑧ CNS: drive Eyes: alertness↑ pupillary dilation Saliva: little,visoous Bronchi: dilation Heart: Skin: rate perspiration foce↑ (cholinergic) blood pre8sure↑ ● Fat tissue: lipolysis fatty acid liberation Liver: glycogenolysis Bladder: glucose release Sphincter tonef detrusor muscle Gl-tract: peristalsis sphincter tonef blood flow Skeletal muscle: blood fow↑ glycogenotysist A.Responses to sympathetic activation
③ Sympathomimetic drugs Adrenergic agonists Adrenoceptor-acti vat ing drugs
Sympathomimetic drugs Adrenergic agonists Adrenoceptor-activating drugs
⑧ Structure-activity relationship 临 B I H-一N 2 B phenylethylamine 》 J80C Catechol
Structure-activity relationship β - phenylethylamine - Catechol
B OH B 6 B HO HO HO. a B B a HC-CH2-NH2 C HC-CH2-NH B HC-CH2-NH OH OL a OH CH3 OH HC-CH内 Norepinephrine Epinephrine laoproterenol CH3 a a 意 a a A.Chemical structure of catecholamines and affinity for 0-and B-receptors Receptor affinity H Catecholamine- O-methyltransferase Penetrability H through I+H Metabolic membrane stability barriers HCc地-N2 OH CH3 (Enteral abeorbability CNS permeability) Monoamine oxidase