A Selective serotonin re-uptake inhibitors

Sumatriptan is a 5HT (serotonin) agonist indicated in the treatment of migraine. Sumatriptan causes vasoconstriction and must therefore be used with caution in patients with coronary heart disease, such as angina. Concurrent administration of the agonist, sumatriptan and antagonists, such as fluoxetine, which is a selective serotonin re-uptake inhibitor, leads to increased CNS toxicity. 

Lorazepam is a short-acting benzodiazepine indicated for use in relieving anxiety and insomnia. Lorazepam may also be administered perioperatively to alleviate pain and in status epilepticus. Imipramine is a tricyclic antidepressant, paroxetine is a selective serotonin re-uptake inhibitor, venlafaxine is a serotonin and adrenaline re-uptake inhibitor and moclobemide is a reversible monoamine oxidase inhibitor. Imipramine, paroxetine, venlafaxine and moclobemide are all classified as antidepressants. 

Furusho J, Matsuzaki K, Ichihashi I, Satoh H, Yamaguchi K, Kumagai K (2001) Alleviation of sleep disturbance and repetitive behavior by a selective serotonin re-uptake inhibitor in a boy with Asperger s syndrome. Brain Dev 23 135-137... 

Fluoxetine is a selective serotonin re-uptake inhibitor (SSRI). The manufacturers of fluoxetine have published a review of the adverse effects that were noted in 1378 patients who took it for up to 2 years (1). 

DU 23000 MK 264 Feverin and many other names) is a compound unrelated to the tricyclics or monoamine oxidase inhibitor ANTIDEPRESSANT classes it is a SSRI, a selective serotonin (re-) UPTAKE INHIBITOR. It is extensively used orally to treat depressive illness, and has the advantage over some other antidepressants in that it has relatively less sedative and anticholinergic side-effects, fluvoxamine maleate fluvoxamine. 

H 102/09 FR 30385 HR 102/09) is a pyridinylpropenamine, a SSRI. a selective serotonin (re-) uptake inhibitor. It moderates ethanol consumption in alcohol-dependent patients and was used as an antidepressant. It is no longer marketed due to adverse effects reported (associated with Guillain-Barr syndrome), zimeldine hydrochloride zimeldine. 

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

A major challenge to the development of new drugs is the discovery of new therapeutic targets. For example, the phenomenal success of fluoxetine (Prozac ) has been due to the fact that it was the first selective serotonin re-uptake inhibitor approved for world market release, combined with its improved adverse drug reaction profile. However, no new classes of antidepressants have emerged in recent years. 

The answer is d. (Kai ung, p 505.) Fluoxetine is a highly selective serotonin re uptake inhibitor (55RI) acting on the 5-1 IT transporter. It forms an active metabolite that is effective for several days. Selective serotonin reuptake inhibitors are inhibitors of cytochrome P450 isoenzymes, which is the basis of potential drug-drug interactions... 

Statins should be avoided in active liver disease and unexplained raised serum transaminases. Some antihistamines, such as diphenhydramine and promethazine, should be used with caution in mild-to-moderate liver disease. Selective serotonin re-uptake inhibitors should be used at a reduced dose or avoided in hepatic impairment. 

Selective serotonin re-uptake inhibitors (SSRIs) and tricyclic antidepressants are equally effective. Hov/ever, SSRIs tend to have fewer antimuscarinic side-effects and are less cardiotoxic in case of overdosage. SSRIs tend to cause gastrointestinal side-effects. Both SSRIs and tricylic antidepressants exhibit a time lag before the action of the antidepressants becomes effective. 

Serotonin mediates many central and peripheral physiological functions, including contraction of smooth muscle, vasoconstriction, food intake, sleep, pain perception, and memory, a consequence of it acting on several distinct receptor types. Although 5-HT may be metabolized by monoamine oxidase, platelets and neurons possess a high-affinity mechanism for reuptake of 5-HT. This mechanism may be inhibited by the widely prescribed antidepressant drugs termed selective serotonin re-uptake inhibitors (SSRl), e.g. fluoxetine (Prozac ), thereby increasing levels of 5-HT in the central nervous system. 

Figure 7. A serotonergic synapse including a depiction of the acute tryptophan depletion method discussed in the text. All large neutral amino acids (SLNAAs) share a common blood-brain barrier transporter. The serotonergic precursor, tryptophan, essentially competes with the other LNAAs for transport. Thus tryptophan is uniquely susceptible to acute dietary manipulation. Numerous serotonergic receptor types exist, including presynaptic S-HTm and (somatodendritic) 5-HTia autoreceptors and postsynaptic 5-HTia, 5-HTid, 5-HT2a 5-HT2c 5-HT3 and 5-HT4 receptors. Additional modulation of serotonin activity can occur via the action of selective serotonin re-uptake inhibitors (SSRls) including fluoxetine, fluvoxamine, and citalopram.

Dmg-induced serotonin syndrome is generally mild and resolves when the offending drugs are stopped. However, it can be severe and deaths have occurred. A large number of drugs have been implicated including tricyclic antidepressants, monoamine oxidase inhibitors (MAOIs), selective serotonin re-uptake inhibitors (SSRIs), pethidine, lithium, and dextromethorphan. The most severe type of reaction has occurred with the combination of selective serotonin re-uptake inhibitors and monoamine oxidase inhibitors. Both non-selective MAOIs such as phenelzine and selective MAOIs such as moclobemide and selegiline have been implicated. 

The structure of the pyridazine-based antidepressant agent minaprine (34-6) departs markedly from both the older tricyclic drugs and the more recent selective serotonin re-uptake inhibitors. There is evidence that the compound acts via a dopa-mimetic route. Friedel-Crafts acylation of benzene with itaconic anhydride (34-1) leads to the keto-acid (34-2). Condensation with hydrazine leads to the formation of the hydrazine and hydrazide bonds the double bond shifts into the ring to give the fully unsaturated pyridazinone (34-3) this is then converted to the chloride (34-4) in the usual way. The displacement of halogen by the amine on 3-(A -morpho-lino)propylamine (34-5) affords (34-6) [36]. 

Szkudlarek J, Elsborg L (1993) Treatment of severe obesity with a highly selective serotonin re-uptake inhibitor as a supplement to a low calorie diet. Int J Obes Relat Metab Disord 17 681-683... 

The diagnosis of depression and the use of antidepressant medication are both associated with an increased risk of myocardial infarction. The relative contribution of these two factors is uncertain. In a case-control study of 2247 subjects, taking antidepressants was associated with a 2.2-fold (Cl = 1.3, 3.7) increase in the risk of myocardial infarction (43). This increased risk seemed to be accounted for entirely by the use of tricyclic antidepressants, because selective serotonin re-uptake inhibitors were not associated with an increased risk, although the confidence intervals were wide (relative risk 0.8 Cl = 0.2, 3.5). These findings support the usual clinical advice that... 

The selective serotonin re-uptake inhibitors (SSRIs) that are currently available are fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, and escitalopram. They are widely marketed and are in many countries a major alternative to tricyclic antidepressants in the treatment of depression. The SSRIs are structurally diverse, but they are all inhibitors of serotonin uptake, with much less effect on noradrenaline. They have slight or no inhibitory effect on histaminergic, adrenergic, serotonergic, dopaminergic, and cholinergic receptors (1). 

The death of a 36-year-old patient with a history of alcohol dependence who was taking tramadol, venlafaxine, trazodone, and quetiapine has highlighted the increased risk of seizures with concomitant use of tramadol and selective serotonin re-uptake inhibitors (125). 

Solomons K, Gooch S, Wong A. Toxicity with selective serotonin re-uptake inhibitors. Am J Psychiatry 2005 162 1225-6. 

Citalopram is a racemic bicyclic phthalane derivative and is a highly selective serotonin re-uptake inhibitor with minimal effects on noradrenaline and dopamine neuronal reuptake. Inhibition of 5-HT re-uptake by citalopram is primarily due to escitalopram, the active S-enantiomer of citalopram (1). One would expect escitalopram to be twice as potent as citalopram but otherwise not to differ significantly from the racemic mixture. However, escitalopram is marketed as being more efficacious than citalopram because, it is argued, the inactive R-isomer present in the racemate actually inhibits binding of the S-enantiomer to its site of action, the serotonin transporter. In some, but not all, clinical trials escitalopram has been statistically superior to citalopram in terms of speed of onset of therapeutic action and improvement on depression rating scales. The clinical significance of these differences is debatable (2). 

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