Page 112 - Basic _ Clinical Pharmacology ( PDFDrive )

98 SECTION II Autonomic Drugs

OH OH

HO CH HO CH HO CH 2
HO CH 2 HO CH 2 HO CH 2
NHCH 3 NH 2 NH 2
Epinephrine Norepinephrine Dopamine
MAO MAO COMT
MAO
OH
HO CH HO CH 2 CH O CH 2
3
COMT COMT
HO C O HO C O HO CH 2
OH OH NH 2
Dihydroxymandelic acid Dihydroxyphenylacetic acid 3-Methoxytyramine
MAO
COMT
OH OH
CH O CH COMT CH O CH CH O CH 2
3
3
3
HO CH 2 HO CH 2 HO C O
NHCH 3 NH 2 OH
Metanephrine Normetanephrine Homovanillic acid
MAO
MAO
OH
CH O CH
3
HO C O
OH
3-Methoxy-4-hydroxy-
mandelic acid
(VMA)

FIGURE 6–6 Metabolism of catecholamines by catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO). (Reproduced, with
permission, from Gardner DG, Shoback D [editors]: Greenspan’s Basic & Clinical Endocrinology, 9th ed. McGraw-Hill, 2011. Copyright © The McGraw-Hill Companies, Inc.)

specific population of neurons can change in response to environ- provides techniques for the discovery and expression of genes that
mental factors such as the light-dark cycle. code for related receptors within these groups (see Chapter 2).
The primary acetylcholine receptor subtypes were named after
the alkaloids originally used in their identification: muscarine
AUTONOMIC RECEPTORS and nicotine, thus muscarinic and nicotinic receptors. In the
case of receptors associated with noradrenergic nerves, the use
Historically, structure-activity analyses, with careful comparisons of of the names of the agonists (noradrenaline, phenylephrine, iso-
the potency of series of autonomic agonist and antagonist analogs, proterenol, and others) was not practicable. Therefore, the term
led to the definition of different autonomic receptor subtypes, adrenoceptor is widely used to describe receptors that respond to
including muscarinic and nicotinic cholinoceptors, and α, β, and catecholamines such as norepinephrine. By analogy, the term cho-
dopamine adrenoceptors (Table 6–2). Subsequently, binding of linoceptor denotes receptors (both muscarinic and nicotinic) that
isotope-labeled ligands permitted the purification and characteriza- respond to acetylcholine. In North America, receptors were col-
tion of several of the receptor molecules. Molecular biology now loquially named after the nerves that usually innervate them; thus,