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

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MAO to monoaminergic nerve terminals. Despite this irreversible
enzyme inhibition, MAOIs require daily dosing.
Adverse Effects
Selective Serotonin Reuptake Inhibitors. The SSRIs, unlike the
TCAs, do not cause major cardiovascular side effects. The SSRIs
are generally free of antimuscarinic side effects (dry mouth, urinary
retention, confusion), do not block histamine or α adrenergic
receptors, and are not sedating (Table 15–4). The favorable side effect
profile of the SSRIs may lead to better patient compliance compared
to that for the TCAs.
SSRIs are not free from side effects, however. Excessive stimulation
of brain 5-HT 2
receptors may result in insomnia, increased
anxiety, irritability, and decreased libido, effectively worsening
prominent depressive symptoms. Excess activity at spinal 5-HT 2
receptors causes sexual side effects including erectile dysfunction,
SECTION II
NEUROPHARMACOLOGY
Table 15–4
Potencies of Selected Antidepressants at Muscarinic, Histamine H 1
, and Alpha 1
Adrenergic Receptors
RECEPTOR TYPE
MUSCARINIC
DRUG CHOLINERGIC HISTAMINE H 1
α 1
ADRENERGIC
Amytriptyline 18 1.1 27
Amoxapine 1000 25 50
Atomoxetine ≥1000 ≥1000 ≥1000
Bupropion 40,000 6700 4550
R,S-Citalopram 1800 380 1550
S-Citalopram 1240 1970 3870
Clomipramine 37 31.2 39
Desipramine 196 110 130
Doxepin 83.3 0.24 24
Duloxetine 3000 2300 8300
Fluoxetine 2000 6250 5900
Fluvoxamine 24,000 >100,000 7700
Imipramine 91 11.0 91
Maprotiline 560 2.0 91
Mirtazapine 670 0.1 500
Nefazodone 11,000 21 25.6
Nortriptyline 149 10 58.8
Paroxetine 108 22,000 >100,000
Protriptyline 25 25 130
Reboxetine 6700 312 11,900
Sertraline 625 24,000 370
Trazodone >100,000 345 35.7
Trimipramine 59 0.3 23.8
Venlafaxine >100,000 >100,000 >100,000
Values are experimentally determined potencies (K i
values, nM) for binding to receptors that contribute to common
side effects of clinically used antidepressant drugs: muscarinic cholinergic receptors (e.g., dry mouth, urinary retention,
confusion), histamine H 1
receptors (sedation), and α 1
adrenergic receptors (orthostatic hypotension, sedation).
Source: Data adapted from Leonard and Richelson (2000).