Serotonin fluoxetine

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]... 

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. 

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... 

Gobert, A, Rivet, JM, Cistarelli, L, Melon, C and Millan, MJ (1997) Alpha2-adrenergic receptor blockade markedly potentiates duloxetine- and fluoxetine-induced increases in noradrenaline, dopamine and serotonin levels in the frontal cortex of freely moving rats. J. Neurochem. 69 2616-2619. 

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. 

We have not explored all of the dose-response relationships. And with respect to the nature of the cue, we have studies underway now with a variety of serotonin agonists and antagonists, for example, fluoxetine. And have looked at MDMA. We eannot bloek the cue with fluoxetine. We are also looking at 8-hydroxy-DPAT, buspirone. PCPA pretreatment is on the way. So there are a variety of manipulations that we have in process. 

QUESTION I have two questions about your MBDB discrimination studies. It sounds as though you are doing experiments to investigate whether neuronal stores of serotonin are required for MBDB to be recognized. You mentioned that fluoxetine did not prevent the recognition. 

ANSWER Actually we used synthesized (-l-)-fenfluramine. The fluoxetine story is not clear. It does not block the discriminative cue, but other workers have shown that it blocks the neurotoxicity. We have not looked at it in enough detail or at any of the in vitro models to see whether it blocks or releases serotonin. 

The data deseribed above demonstrate that destruction of serotonin axons by MDMA involves the serotonin aetive uptake carrier and that administration of citalopram, a selective serotonin uptake blocker, prior to administration of MDMA, ean prevent the decreases in serotonin markers elicited by MDMA alone. These data are eonsistent with previous reports for other potent serotonin neurotoxins, demonstrating that pretreatment with serotonin uptake blockers can prevent the neurotoxic effects of parachloroamphetamine (Ross 1976 Sanders-Bush and Steranka 1978). Furthermore, it has been shown that MDMA-induced neurotoxicity can be prevented or reversed if a serotonin uptake blocker such as fluoxetine is administered no later than 12 hours after MDMA treatment (Schmidt 1986). 

The selective serotonin reuptake inhibitors (SSRIs) paroxetine, fluoxetine, and sertraline are potentially useful due to... 

The first-line therapeutic options for PMDD include the selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine, fluvoxamine, sertraline, paroxetine, and citalopram. These agents can be given either continuously or only during the luteal phase of the menstrual cycle, i.e., initiated at the time of ovulation and discontinued on the first day of menses. 

Altered removal of a neurotransmitter from the synaptic cleft. The third mechanism by which drugs may alter synaptic activity involves changes in neurotransmitter reuptake or degradation. A very well known example of a drug in this category is Prozac (fluoxetine), which is used to treat depression. The complete etiology is unknown, but it is widely accepted that depression involves a deficiency of monoamine neurotransmitters (e.g., norepinephrine and serotonin) in the CNS. Prozac, a selective serotonin reuptake inhibitor, prevents removal of serotonin from the synaptic cleft. As a result, the concentration and activity of serotonin are enhanced. 

Kalia, M., O Callaghan, J.R, Miller, D.B., and Kramer, M., Comparative study of fluoxetine, sibutra-mine, sertraline and dexfenfluramine on the morphology of serotonergic nerve terminals using serotonin immunohistochemistry, Brain Res. 858(1), 92-105, 2000. 

Many neurotransmitters are inactivated by a combination of enzymic and non-enzymic methods. The monoamines - dopamine, noradrenaline and serotonin (5-HT) - are actively transported back from the synaptic cleft into the cytoplasm of the presynaptic neuron. This process utilises specialised proteins called transporters, or carriers. The monoamine binds to the transporter and is then carried across the plasma membrane it is thus transported back into the cellular cytoplasm. A number of psychotropic drugs selectively or non-selectively inhibit this reuptake process. They compete with the monoamines for the available binding sites on the transporter, so slowing the removal of the neurotransmitter from the synaptic cleft. The overall result is prolonged stimulation of the receptor. The tricyclic antidepressant imipramine inhibits the transport of both noradrenaline and 5-HT. While the selective noradrenaline reuptake inhibitor reboxetine and the selective serotonin reuptake inhibitor fluoxetine block the noradrenaline transporter (NAT) and serotonin transporter (SERT), respectively. Cocaine non-selectively blocks both the NAT and dopamine transporter (DAT) whereas the smoking cessation facilitator and antidepressant bupropion is a more selective DAT inhibitor. 

Fluoxetine The first clinically available selective serotonin reuptake inhibitor (SSRI). 

Selective serotonin reuptake inhibitor (SSRI) Currently, the most widely used antidepressants (e.g., fluoxetine and paroxetine). 

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. 

Since the introduction of fluoxetine (3) in 1987, a series of selective serotonin reuptake inhibitors (SSRIs) have been discovered that have seen broad application in many facets of mood disorders. These compounds include fluvoxamine (4) which contains a trifluoromethyl group and paroxetine (5) and citalopram (6) which contain 4-fluorophenyl groups [5,6]. 

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