DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

Table 14–5
Dopamine Receptors in the CNS
G-PROTEIN
RECEPTOR AGONISTS ANTAGONISTS FAMILY AREAS OF LOCALIZATION
D 1
SKF82958 SCH23390 G s
neostriatum; cerebral cortex;
SKF81297 SKF83566; haloperidol olfactory tubercle; nucleus accumbens
D 2
Bromocriptine, Raclopride, sulpiride, G i
neostriatum; olfactory tubercle;
apomorphine haloperidol nucleus accumbens
D 3
Quinpirole Raclopride G i
nucleus accumbens; islands of Calleja
7-OH-DPAT
D 4
Clozapine, L-745,870, G i
midbrain; amygdala; hippocampus;
sonepiprazole
hypothalamus
D 5
SKF38393 SCH23390 G s
7-OH-DPAT, 7-hydroxy-N,N-di-n-propyl-2-aminotetralin.
hippocampus. However, this catecholamine also is present in significant,
although lower, amounts in most brain regions. Detailed mapping
studies indicate that noradrenergic neurons of the locus ceruleus
innervate specific target cells in a large number of cortical, subcortical,
and spinomedullary fields (Nestler et al., 2009). NE has been
established as the transmitter at synapses between presumptive noradrenergic
pathways and a wide variety of target neurons. For example,
stimulation of the locus ceruleus depresses the spontaneous activity
of target neurons in the cerebellum; this is associated with a slowly
developing hyperpolarization and a decrease in membrane conductance
(Aston- Jones et al., 2001; Nestler et al., 2009).
Multiple types and subtypes of adrenergic receptors (α 1
, α 2
,
and β) and their subtypes have been described in the CNS; all are
GPCRs (Table 14–6). As expected, β receptors couple to G s
and
Table 14–6
Adrenergic Receptors in the CNS
G-PROTEIN AREAS OF LOCALIZATION
RECEPTOR AGONIST ANTAGONIST FAMILY IN THE BRAIN
α 1A
A61603 nigulpidine G q
cortex, hippocampus
phenylephrine prazosin
oxymetazoline 5-methylurapidil
α 1B
phenylephrine spiperone G q
cortex
oxymetazoline prazosin (+)-cyclazosin brainstem
α 1D
phenylephrine A-119637 G q
cortex
oxymetazoline tamsulosin
α 2A
oxymetazoline yohimbine; rauwolscine; G i
locus ceruleus and hippocampus
clonidine
bromocriptine
α 2B
clonidine yohimbine; rauwolscine; G i
diencephalon
dexmedetomidine lisuride
α 2C
clonidine yohimbine; rauwolscine; G i
widely distributed
lisuride
β 1
CGP 12177 alprenolol G s
cortex and hypothalamus
prenalterol
betaxolol
metoprolol
β 2
fenoterol propranolol G s
cerebellum, hippocampus, cortex
salmeterol ICI 118551
β 3
carazolol carvedilol; tertalolol ? G s
unknown