ABSTRACT
Paroxetine is a potent and selective serotonin reuptake inhibitor (SSRI) with currently approved indications for the treatment of depression, obsessive-compulsive disorder, panic disorder and social phobia. It is also used in the treatment of generalized anxiety disorder, post traumatic stress disorder, premenstrual dysphoric disorder and chronic headache. Paroxetine, a phenylpiperidine derivative, is the most potent inhibitor of the reuptake of serotonin (5-hydroxytryptamine, 5-HT) of all the currently available antidepressants including the class of SSRIs. It is a very weak inhibitor of norepinephrine (NE) uptake but it is still more potent at this site than the other SSRIs. The selectivity of paroxetine, i.e., the ratio of inhibition of uptake of norepinephrine to serotonin (NE/5-HT) is amongst the highest of the SSRIs. Paroxetine has little affinity for catecholaminergic, dopaminergic or histaminergic systems and by comparison with tricyclic antidepressants (TCAs) has, therefore, a reduced propensity to cause central and autonomic side effects. Paroxetine exhibits some affinity for the muscarinic cholinergic receptor but much less than the TCAs. In addition, the adaptive changes of somatodendritic (5-HT(1A)) and terminal (5-HT(1B/1D)) autoreceptors observed with paroxetine are different to those observed with TCAs; it also inhibits nitric oxide synthase. It is both a substrate and an inhibitor of cytochrome isoenzyme P450 2D6. Paroxetine is well absorbed orally and undergoes extensive first pass metabolism that is partially saturable. Its metabolites are pharmacologically inactive in vivo. Steady state levels are achieved after 4-14 days and an elimination half-life of 21 h is consistent with once-daily dosing. There is wide inter-individual variation in the pharmacokinetics of paroxetine in adults as well as in the young and the elderly with higher plasma concentrations and slower elimination noted in the latter. Elimination is also reduced in severe renal and hepatic impairment. Serious adverse events are, however, extremely rare even in overdose. In summary, paroxetine is well tolerated and effective in the treatment of both depressive and anxiety disorders across the age range.
Subject(s)
Antidepressive Agents, Second-Generation/pharmacology , Antidepressive Agents, Second-Generation/therapeutic use , Mental Disorders/drug therapy , Paroxetine/pharmacology , Paroxetine/therapeutic use , Selective Serotonin Reuptake Inhibitors/pharmacology , Selective Serotonin Reuptake Inhibitors/therapeutic use , Animals , Antidepressive Agents, Second-Generation/adverse effects , Antidepressive Agents, Second-Generation/pharmacokinetics , Humans , Mental Disorders/psychology , Paroxetine/adverse effects , Paroxetine/pharmacokinetics , Selective Serotonin Reuptake Inhibitors/adverse effects , Selective Serotonin Reuptake Inhibitors/pharmacokineticsSubject(s)
Anti-Anxiety Agents/pharmacology , Dentistry, Operative , Piperazines/pharmacology , Stress, Psychological/drug therapy , Adult , Anti-Anxiety Agents/administration & dosage , Clorazepate Dipotassium/administration & dosage , Clorazepate Dipotassium/pharmacology , Drug Evaluation , Female , Humans , Male , Middle Aged , Naphthyridines , Piperazines/administration & dosage , Stress, Psychological/diagnosis , Sulfur CompoundsABSTRACT
In normal fetuses from day 16 to 21 of pregnancy, unbound plasma corticosterone concentration increases slowly from day 16 to 17, and rapidly from day 17 to 19, remaining high until birth. Fetal decapitation on day 18 produces a fall in unbound plasma corticosterone only when the mother is adrenalectomized. The ability of corticosterone to cross the placental barrier from mother to fetus or inversely is discussed.
