Summary Adrenoceptors a receptors a, receptors: vasoconstriction increased peripheral resistance, BPT; contraction of radial muscle of iris: mydriasis a2 receptors: CNS, presynaptic membranes of adrenergic nerves: vasodilatation, inhibition of NE release: inhibition of insulin release
receptors • 1 receptors: vasoconstriction: increased peripheral resistance, BP↑; contraction of radial muscle of iris: mydriasis • 2 receptors: CNS, presynaptic membranes of adrenergic nerves: vasodilatation, inhibition of NE release; inhibition of insulin release Summary: Adrenoceptors 11
Summary: Adrenoceptors β Receptors β1 receptors: heart stimulation: contractility↑, automaticity个↑, conduction↑, oxygen- consumption↑, cardiac output; increased lipolysis B2receptors: bronchodilation; slight vasodilation increased muscle and liver glycogenolysis; increased release of glucagon B3receptors: 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, am phetamine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 efficacy HO CH-CH,-N COMT sensitive short duration H H0)|· No entry to CNS HO HO Norepinephrine Dopamine HO CH-CH2-NHz OH HO CH-CH2-N Norepinephrine HO Epinephrine 32 4 CH2-CH3-NHa 56 OH 苯乙胺 CNS entry HO H-CH,-N Resistant to mAo Pheny ethylamine CH HO CH一CH一NH—CH c Isoproterenol H OH(CH CH2麻黄碱phet CH Affinity for B receptors Increases as group 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 ali, a2 receptor agonists CH-CH2--NHz (1)Vascular effects a1: vasoconstriction(skin, renal, brain, hepatic, mesenteric, etc ) blood flow l a2: 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