Serotonin uptake inhibitors

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]... 

Naranjo CA, Sellers EM, Chater K, et al Non-pharmacological interventions in acute alcohol withdrawal. Clin Pharmacol Ther 34 214—219, 1983 Naranjo CA, Sellers EM, Roach CA, et al Zimelidine-induced variations in alcohol intake hy nondeptessed heavy drinkers. Clin Pharmacol Ther 35 374-381, 1984 Naranjo CA, Sellers EM, Sullivan ]T, et al The serotonin uptake inhibitor citalopram attenuates ethanol intake. Clin Pharmacol Ther 41 266-274, 1987 Naranjo CA, Sullivan ]T, Kadlec KE, et al Differential effects of viqualine on alcohol intake and other consummatory behaviors. Clin Pharmacol Ther 46 301 -309,1989 Naranjo CA, Kadlec KE, Sanhueza P, et al Fluoxetine differentially alters alcohol intake and other consummatory behaviors in problem drinkers. Clin Pharmacol Ther 47 490 98, 1990... 

However, the specific serotonin uptake inhibitor fluoxetine failed to produce an MBDB-like cue and failed to block the stimulus effects of MBDB when it was given prior to a training dose of MBDB. Table 3 summarizes results of fluoxetine testing in MBDB-trained rats. In other exploratory studies, pretreatment of MDMA-trained rats with either methysergide or ketanserin failed to block completely the MDMA-discriminative stimulus. 

Plants affecting the serotoninergic neurotransmission are therefore interesting because of their potentials for the treatment of depression, which is the eighth leading cause of death in the United States. It is generally agreed that there is a correlation between diminished serotonin neurotransmission and episodes of major depression, and a number or inhibitors of serotonin-uptake inhibitors are available on the market, such as sertraline (Zoloft ). 

Liechti, M.E. and Vollenweider, F.X., The serotonin uptake inhibitor citalopram reduces acute cardiovascular and vegetative effects of 3,4-methylenedioxymethamphetamine ( Ecstasy ) in healthy volunteers, J. Psychopharmacol. 14(3), 269-274, 2000. 

Savage, D. D., Mendels, J., and Frazer, A. (1980) Monoamine oxidase inhibitors and serotonin uptake inhibitors Differential effects on [3H]serotonin binding sites in rat brain. J. Pharmacol. Exp. Ther., 212 259-263. 

The radiosynthesis of [ F] fluoxetine, a selective serotonine uptake inhibitor (Scheme 62), is one of the rare examples in which a Br atom has been substituted for an F isotope [248]. It suffers from a low specific radioactivity due to decomposition of starting material. 

The bioreduction of carbonyl compounds with reductases has been exploited for many years, especially in the case of ketones, with baker s yeast Saccharomyces cerevisiae) being the most popular biocatalyst [45]. For instance, yeast treatment of 3-chloropropiophenone affords the expected (lS)-3-chloro-l-phenylpropan-l-ol, which was treated with trifluorocresol in tertrahydrofuran in the presence of tri-phenylphosphine and diethyl azodicarboxylate at room temperature to give (3R)-l-chloro-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propane and the later reaction with methylamine leads to (R)-fluoxetine that is an important serotonin uptake inhibitor (Scheme 10.19) [46]. 

Bupropion is an a-aminoketone that is structurally related to amphetamines, and it exhibits unique activity comparable to that of other antidepressants. It is believed that bupropion restores the total amount of norepinephrine in the body. This compound is a poor reuptake inhibitor of dopamine, and does not exhibit anticholinergic activity or inhibit MAO. Its efficacy as an antidepressant is comparable to that of tricyclic antidepressants, and as a serotonin uptake inhibitor it is comparable to fluoxetine. It is preferable to use amoxapine. Synonyms of bupropion are amphebutamon and wellbutrin. 

Boyer W (1995) Serotonin uptake inhibitors are superior to imipramine and alprazolam in alleviating panic attacks a metaanalysis. Int Clin Psychopharmacol 10 45-49 Bradwejn J, Koszycki D (1994) Imipramine antagonism of the paniogenic effects of chole-cystokinin tetrapeptide in panic disorder patients. Am J Psychiatry 151 261-263 Bradwejn J, Koszycki D, Paradis M, Reece P, Hinton J, Sedman A (1995) Effect of CI-988 on cholecystokinin tetrapeptide-induced panic symptoms in healthy volunteers. Biol Psychiatry 38 742-746... 

Selegiline should not be coadministered with tricyclic antidepressants or selective serotonin uptake inhibitors because of the possibility of a severe adverse drug reaction (e.g., hyperpyrexia, agitation, delirium, coma). 

Another pharmacological approach is the use of anticraving drugs, for example serotonin uptake inhibitors,... 

Hostetter, A., Stowe, Z.N., Strader, J.R., Jr., McLaughlin, E., Llewellyn, A. (2001) Dose of selective serotonin uptake inhibitors across pregnancy clinical implications. Depress Anxiety, 11 51-57. 

Hrdina, P.D. (1991) Pharmacology of serotonin uptake inhibitors focus on fluvoxamine. / Psychiatry Neurosci 16(Suppl 1) 10-18. 

Wong, D.T., Fuller, R.W., and Robertson DW. (1990) Fluoxetine and its two enantiomers as selective serotonin uptake inhibitors. Acta Pharm Nord 2 171-180. 

Studies of the use of the specific serotonin-uptake inhibitors (SSRIs) to treat OCD suggest that, compared to non-tic-related OCD, tic-related OCD is less responsive to SSRI monotherapy (McDougle et al., 1993, 1994). Addition of a neuroleptic, such as haloperidol (McDougle et ah, 1994), risperidone (McDougle et al., 2000), or olanzapine (Bogetto et al., 2000), appears to be useful in improving treatment-resistant individuals response to a SSRI. It is unclear whether this pattern of treatment response is specifically associated with a comorbid tic disorder the pattern of obsessive compulsive symptoms characteristic of TS or yet some other predictors. 

TABLE 15-1B. Compounds marketed since 1990 or under development as selective or combination norepinephrine/serotonin uptake inhibitors or selective monoamine oxidase inhibitors [MAOIs]... 

As already noted, initiating treatment with the combination of an Oj antagonist with a norepinephrine uptake inhibitor (or serotonin uptake inhibitor... 

Boyer W Serotonin uptake inhibitors are superior to omopramine and alprazolam in alleviating panic attacks a meta-analysis. Int Clin Psychopharmacol 10 45-49,... 

Saletu B, Frey R, Krupka M, et al Sleep laboratory studies on the single-dose effects of serotonin uptake inhibitors paroxetine and fluoxetine on human sleep and waking qualities. Sleep 14 439-447, 1991... 

Tohgi H, Abe T, Takahashi S, et al Indoleamine concentrations in cerebrospinal fluid from patients with Alzheimer type and Binswanger type dementias before and after administration of citalopram, a synthetic serotonin uptake inhibitor. J Neural Transm 9 121-131, 1995... 

Shuey DL, Sadler TW, Lauder JM. Serotonin as a regulator of craniofacial morphogenesis site specific malformations following exposure to serotonin uptake inhibitors. Teratology 1992 46 367-378. 

Den Boer JA, Westenberg HGM, Kamerbeek WDJ, et al. Effect of serotonin uptake inhibitors in anxiety disorders a double-blind comparison of clomipramine and fluvoxamine. IntClin Psychopharmacol 1987 2 21-32. 

Chouinard G, Goodman W, Greist J, et al. Results of a double-blind placebo controlled trial of a new serotonin uptake inhibitor, sertraline, in the treatment of obsessive-compulsive disorder. Psychopharmacol Bull 1990 26 279-284. 

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