Selective serotonin inhibitors

Goodnick PL and Goldstein BJ. Selective serotonin inhibitors in affective disorders I. Basic pharmacology. J Psychopharmacol 1998 12 S5-20. 

Since IL-6 stimulates Prostaglandin E2 (PGE2) and antidepressants inhibit the IL-6 production, an inhibiting action of antidepressants on PGE2 would be expected, too (Poliak and Yirmiya, 2002). Over twenty years ago it was suggested that antidepressants inhibit PGE2 (Mtabaji et al., 1977). A recent in-vitro study showed that both tricyclic antidepressants and selective serotonin inhibitors attenuated cytokine-induced PGE2 and nitric oxide production by inflammatory cells (Yaron et al., 1999). 

The first major groups of antidepressant medications are the tricyclics, also known as the TCAs. Discovered in the late 1950s, these drugs are considered the oldest in the treatment of depression and have historically been used as the first line of medication intervention for the treatment of unipolar depression (Austrian, 1995). The side-effect profile that accompanies this group of medications, however, has recently caused them to fall into disfavor. For years, these medications were often considered the first choice for the client who suffers from depressed mood. Today, however, the antidepressant medications known as the selective serotonin inhibitors (SSRIs), and the selective serotonin norepinephrine inhibitors (SSNRIs) are often considered as the first-line medications. 

Beginning in the 1960s, ben2odia2epiae anxiolytics and hypnotics rapidly became the standard prescription dmg treatment. In the 1980s, buspkone [36505-84-7] (3), which acts as a partial agonist at the serotonin [50-67-9] (5-hydroxytryptamine, 5-HT) type lA receptor, was approved as treatment for generali2ed anxiety. More recently, selective serotonin reuptake inhibitors (SSRIs) have been approved for therapy of panic disorder and obsessive—compulsive behavior. 

Treatment of Major Depression. Dmgs commonly used for the treatment of depressive disorders can be classified heuristicaHy iato two main categories first-generation antidepressants with the tricycHc antidepressants (TCAs) and the irreversible, nonselective monoamine—oxidase (MAO) inhibitors, and second-generation antidepressants with the atypical antidepressants, the reversible inhibitors of monoamine—oxidase A (RIMAs), and the selective serotonin reuptake inhibitors (SSRIs). Table 4 fists the available antidepressants. 

Selective Serotonin Reuptake Inhibitors. In 1987, the FDA approved fluoxetine [54910-89-3] (42) for use in the treatment of major... 

Two recently introduced antidepressants are notable m that they are selective serotonin uptake inhibitors Citalopram (19) is reported to be as effective as amitriptyline m the treatment of endogenous depression [75, 16] Fluoxetine (20) as the hydrochlonde is approved for major depressive disorders mcludmg those with concomitant anxiety Interestmgly, it also appears useful m the treatment of obesity [17]... 

MDMA overdose as well as the concomitant consumption of selective serotonin reuptake inhibitors (SSRI) with other dmgs that exert serotoninergic effects (such as inhibitors of monoamine oxidase) can rapidly lead to the serotonin syndrome. Its symptoms, which are reversible upon cessation, of the drug include confusion, muscle rigidity in the lower limbs, and hyperthermia suggesting an acute reaction to serotonin overflow in the CNS. Blocking the function of SERT outside the brain causes side effects (e.g., nausea), which may be due to elevated 5HT however , impairment of transporter function is not equivalent to direct activation of 5HT recqrtors in causing adverse effects such as fibrosis and pulmonary hypertension. 

Selective serotonine reuptake inhibitor (SSRI) is an abbreviation for the class of antidepressants known as the Selective Serotonin Reuptake Inhibitors. Examples of SSRIs include fluoxetine, paroxetine, citalopram, and sertraline. These drugs selectively inhibit the serotonin transporter thus prolonging the synaptic lifespan of the neurotransmitter serotonin. 

Indeed, 5-HT is also a substrate for the 5-HT transporter, itself an important player in the treatment of depression, and more recently for the whole range of anxiety disorders spectrum (GAD, OCD, social and other phobias, panic and post-traumatic stress disorders). It is the target for SSRIs (selective serotonin reuptake inhibitors) such as fluoxetine, paroxetine, fluvoxamine, and citalopram or the more recent dual reuptake inhibitors (for 5-HT and noradrenaline, also known as SNRIs) such as venlafaxine. Currently, there are efforts to develop triple uptake inhibitors (5-HT, NE, and DA). Further combinations are possible, e.g. SB-649915, a combined 5-HTia, 5-HT1b, 5-HT1d inhibitor/selective serotonin reuptake inhibitor (SSRI), is investigated for the treatment of major depressive disorder. 

VMATs are not inhibited by drugs such as cocaine, tricyclic antidqnessants and selective serotonin reuptake inhibitors that affect plasma membrane monoamine transport. Amphetamines have relatively selective effects on monoaminergic cells due to selective uptake by plasma membrane monoamine transporters, but their effect appears to be mediated by their ability as weak bases to reduce ApH, the driving force for vesicular monoamine transport that leads to efflux of the vesicular contents into the cytoplasm. 

Antidepressants Trazodone, mirtazapine, paroxetine, other selective serotonin reuptake inhibitors venlafaxine... 

Patients seen for flashbacks are treated with oral diazepam (15—30 mg/day for adults) if symptoms of anxiety are severe (Rumack 1987). Neuroleptics, especially haloperidol, have been implicated in a transient increase in visual flashbacks and are not recommended (Moskowitz 1971 Strassman 1984). Risperidone and selective serotonin reuptake inhibitors may also worsen symptoms of hallucinogen persisting perception disorder (Halpern and Pope 2003). The patient needs assurance of the self-limiting nature of the phenomenon and its decreasing frequency of reoccurrence with time. The patient should be reminded that any future use of hallucinogens or marijuana may precipitate similar symptoms (Strassman 1984). 

Briggs G, Freeman R, Yaffe S Drugs in Pregnancy and Lactation A Reference Guide to Maternal and Fetal Risk. Philadelphia, Lippincott, Williams Wilkins, 2002 Chengappa KN, Kambhampati R, Perkins K, et al Bupropion sustained release as a smoking cessation treatment in remitted depressed patients maintained on neatment with selective serotonin reuptake inhibitor antidepressants. J Clin Psychiatry 62 503—508, 2001... 

The enantiomerically pure 3-arylglutaric ester are precursors for the synthesis of (—)-paroxetine [10], a selective serotonin reuptake inhibitor used in the treatment of depression, obsessive compulsive disorder, and panic, and (i )-Baclofen [11], a GABAb receptor agonist, which is used cHnically in the treatment of spasticity (Chart 5.1). 

The main focus of pharmacoeconomic studies of antidepressants has inevitably fallen on comparisons between tricyclic antidepressants (TCAs) and the more expensive selective serotonin reuptake inhibitors (SSRIs). Few data are available for comparisons within the SSRIs or for newer antidepressants. 

Anderson IM, Tomenson BM (1994). The efficacy of selective serotonin reuptake inhibitors in depression a meta-analysis of studies against tricyclic antidepressants. / Psychopharmacol 8, 238 9. 

CCOHTA] Canadian Coordinating Office for Health Technology Assessment (1997). Selective Serotonin Re-uptake Inhibitors (SSRIs) for Major DepressionyVdJxll The Cost-... 

Donoghue JM (1998). Selective serotonin re-uptake inhibitor use in primary care a five year naturalistic study. Clin Drug Invest 16, 453-62. 

Selective serotonin reuptake inhibitor antidepressant selection and anxiolytic and sedative hypnotic prescribing a multivariate analysis./ Clin Outcomes Manage 4, 16—22. 

Selective serotonin reuptake inhibitors metaanalysis of efficacy and acceptability. Br Med J 306,683-7. 

Sechter D, Lane RM (1997). Continuation therapy with selective serotonin re-uptake inhibitors./... 

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