文档介绍：1、肾上腺素能神经系统
(1)肾上腺素受体激动药
(2)肾上腺素受体拮抗药
2、镇静催眠药
2014-10-13
本次课内容
张纬萍
******@zju.
药理学系
Adrenergic Pharmacology
Noradrenergic Nerve:
Synthesis, storage
and release of NE
Tyrosine
tyrosine hydroxylase (TH)
L-DOPA
DOPA decarboxylase
dopamine (DA)
dopamine beta-hydroxylase (DBH)
norepinephrine (NE)
Uptake
neurotransmitter transporters
uptake 1: neuronal uptake
uptake 2: non-neuronal uptake
Enzymatic degradation
monoamine oxidase (MAO)
catechol-O-methyltransferease
(COMT)
Regulation of NE Synthesis and Turnover
Catecholamine Biosynthetic Pathway
rate limiting
2 receptor
2 receptor
Presynaptic autoreceptor
Presynaptic heteroreceptor
Ach_reduce
Norepinephrine and Epinephrine
Synthesis in the Adrenal Medulla
NE is stored in vesicles
DBH is located in vesicles
PNMT(苯乙胺N甲基转移酶)is located in the cytosol .
EPI is stored in vesicles
- EPI (~80%) and NE (~20%) released into blood
Chromaffin cell肾上腺嗜铬细胞
NE
PNMT
NE
EPI
EPI
EPI disposition: metabolism T(儿茶酚-O-甲基转移酶), MAO, sulfation, uptake into NE terminals
NE Metabolism
MHPG: was used as
an index S NE turnover
but generated mostly from periphery
VMA: sometimes used as
an index of NE turnover
Sulfate conjugates
also prevalent
Adrenergic Receptors/Adrenoceptors
1
2
1
G-Protein Coupled Receptors
Norepinephrine (NE) release
signal transduction
response
receptor binding (reversible)
receptor activation
(2
3)
low affinity for binding NE
Adrenergic Receptor (adrenoreceptors)
These are receptors activated by NE, EPI, or drugs with similar actions
b3
fat cells
(not NE)
Gq
Gi
Gs
Gs
Structure-activity relationship of
catecholamines and pounds
b-receptor
activity
麻黄碱
苯乙胺
Bioavailability of oral admin.
Duration.
CNS distribution
Block MAO
uptake-1
For activation of receptor
Resistance to MAO