Summary: Adrenoceptors β Receptors Preceptors: heart stimulation: contractility automaticity↑, conduction↑, OXygen- consumption↑, cardiac output: increased lipolysis B2 receptors: bronchodilation; slight vasodilation increased muscle and liver glycogenolysis; increased release of glucagon °β3 receptors: lipolysis, thermogenesis 12
b Receptors • b1 receptors: heart stimulation: contractility↑, automaticity↑, conduction↑, oxygen-consumption↑, cardiac output↑; increased lipolysis • b2 receptors: bronchodilation; slight vasodilation; increased muscle and liver glycogenolysis; increased release of glucagon • b3 receptors: lipolysis, thermogenesis Summary: Adrenoceptors 12
Drug classification 1. Direct actions on the receptors Agonists(NE, EPl, Iso, dopamine, etc) Antagonists(phentolamine, propranolol, etc 2 Indirect actions via affecting transmitters Synthesis( L-dopa) Transport and storage( ImipramIne丙咪嗪, reserpine利舍平) Release( ephedrine麻黄碱, amphetamine安非他明) Inactivation MAOl) 13
Drug classification 1. Direct actions on the receptors Agonists (NE, EPI, ISO, dopamine, etc) Antagonists (phentolamine, propranolol, etc) 2 Indirect actions via affecting transmitters Synthesis (L-dopa) Transport and storage (imipramine丙咪嗪, reserpine 利舍平) Release (ephedrine 麻黄碱, amphetamine 安非他明) Inactivation (MAOI) 13
Adrenergic agonists catecholamines and related compounds OH HO Strong efficac HO CH-CHo-N COMT sensitive, short duration HO No entry to CNS HO OH Norepinephrine Dopamine HO OH HO H-cH。-N c Norepinephrine HO Epinephrine 32 CH2-CH2- NHz H 苯乙胺 CNS ent HO Resistant to mao Phenylethyl CH HO CH一CH-NH—CH3 c Isoproterenol H OH CH N CH麻黄碱heth CH ffinity for B recept Inc on amIne nItrogen gets larger. Methamphetamine 14 甲基苯丙胺
Structure-activity relationship of catecholamines and related compounds 苯乙胺 麻黄碱 • Strong efficacy • COMT sensitive, short duration • No entry to CNS • CNS entry • Resistant to MAO Methamphetamine 甲基苯丙胺 Adrenergic agonists 14 Dopamine
Norepinephrine, Noradrenaline Pharmacological effects: OH a1, a2 receptor agonists CH-CH2-NHz (1)Vascular effects a,: vasoconstriction(skin, renal, brain, hepatic, mesenteric, etc ) blood flow l 2: inhibiting NE release (2) Blood pressure Systolic BPT, Diastolic BP T(especially at larger doses 15
Norepinephrine, Noradrenaline Pharmacological effects: 1 , 2 receptor agonists (1) Vascular effects： 1：vasoconstriction (skin, renal, brain, hepatic, mesenteric, etc.), blood flow 2：inhibiting NE release (2) Blood pressure： Systolic BP , Diastolic BP (especially at larger doses) 15
Norepinephrine (3 Cardiac effects weak direct stimulation (B1) inhibition via reflex ( in vivo Net result little cardiac stimulates 180 Norepinephrine mean Arterial 140 Pressure (mmHg) 100 120 Heart 100 Rate beats/min) 80 60 16 Time(min
(3) Cardiac effects： weak direct stimulation (b1 ); inhibition via reflex (in vivo) Net result: little cardiac stimulates Norepinephrine 16