Fluoxetine effects

Goldberg MJ, Bergstrom RF, Cerimele BJ, Thomassom HR, Hatcher BL, Simcox EA. Fluoxetine effects on pindolol pharmacokinetics. Clin Pharmacol Ther 991)6, 178. 

Carson SW, Letrent KJ, Kotlyar M, Foose G, Tancer ME. Lack of fluoxetine effect on prednisolone disposition and cortisol suppression. Pharmacotherapy (2004) 24,482-7. 

SSRIs are widely used for treatment of depression, as well as, for example, panic disorders and obsessive—compulsive disorder. These dmgs are well recognized as clinically effective antidepressants having an improved side-effect profile as compared to the TCAs and irreversible MAO inhibitors. Indeed, these dmgs lack the anticholinergic, cardiovascular, and sedative effects characteristic of TCAs. Their main adverse effects include nervousness /anxiety, nausea, diarrhea or constipation, insomnia, tremor, dizziness, headache, and sexual dysfunction. The most commonly prescribed SSRIs for depression are fluoxetine (31), fluvoxamine (32), sertraline (52), citalopram (53), and paroxetine (54). SSRIs together represent about one-fifth of total worldwide antidepressant unit sales. 

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]... 

Fig. 2-16. The effect of organic modifiers on the resolution of fluoxetine enantiomers on vancomycin CSP (250 X 4.6 mm). The flow rate was 1.0 mL min at ambient temperature (23 °C). (Courtesy of Scott Sharpe, Eli Lilly Co.)...

More dramatic examples of how a change in chirality can affect the biological properties of a molecule are found in many drugs, such as fluoxetine, a heavily prescribed medication sold under the trade name Prozac. Racemic fluoxetine is an extraordinarily effective antidepressant but has no activity against... 

Antidepressants are used in the treatment of neuropathic pain and headache. They include the classic tricyclic compounds and are divided into nonselective nor-adrenaline/5-HT reuptake inhibitors (e.g., amitriptyline, imipramine, clomipramine, venlafaxine), preferential noradrenaline reuptake inhibitors (e.g., desipramine, nortriptyline) and selective 5-HT reuptake inhibitors (e.g., citalopram, paroxetine, fluoxetine). The reuptake block leads to a stimulation of endogenous monoaminer-gic pain inhibition in the spinal cord and brain. In addition, tricyclics have NMDA receptor antagonist, endogenous opioid enhancing, Na+ channel blocking, and K+ channel opening effects which can suppress peripheral and central sensitization. Block of cardiac ion channels by tricyclics can lead to life-threatening arrhythmias. The selective 5-HT transporter inhibitors have a different side effect profile and are safer in cases of overdose [3]. 

There is a decreased effectiveness of fluoxetine in patients who smoke cigarettes during administration of die drug. Fluoxetine is not administered witii lithium because this combination can increase lithium levels. The SSRIs are not administered witii herbal preparations containing St. Jbhn s wort because tiiere is an increased risk for severe reactions. 

The effects of buspirone are decreased when the drug is administered with fluoxetine Increased serum levels of buspirone occur if the drug is taken with erythromycin or itraconazole Should any of these combinations be required, the dosage of buspirone is decreased to 2.5 mg BID, and the patient is monitored closely. Venlafaxine blood levels increase with a risk of toxicity when administered witii MAOIs or cimetidine There is an increased risk of toxicity when trazodone is administered with the phenothiazines and decreased effectiveness of trazodone when it is administered with carbamazepine Increased serum digoxin levels have occurred when digoxin is administered with trazodone There is a risk for increased phenytoin levels when phenytoin is administered witii trazodone... 

Gorelick DA, Paredes A Effect of fluoxetine on alcohol consumption in male alcoholics. Alcohol Clin Exp Res 16 261-265, 1992... 

Kranzler HR, Del Boca F, Korner P, et ah Adverse effects limit the usefulness of flu-voxamine for the treatment of alcoholism.] Subst Abuse Treat 10 283-287, 1993 Kranzler HR, Burleson JA, Del Boca FK, et ah Buspirone treatment of anxious alcoholics a placebo-controlled trial. Arch Gen Psychiatry 31 720—731, 1994 Kranzler HR, Burleson JA, Korner P, et ah Placebo-controlled trial of fluoxetine as an adjunct to relapse prevention in alcoholics. Am] Psychiatry 152 391-397, 1995 Kranzler HR, Burleson JA, Brown J, et al Fluoxetine treatment seems to reduce the beneficial effects of cognitive-behavioral therapy in type B alcoholics. Alcohol Clin Exp Res 20 1534-1341, 1996... 

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... 

Antidepressants Desipramine, imipramine, sertraline, fluoxetine, paroxetine, venlafaxine, bupropion, nefazodone, mirtazapine, gepirone, amineptine Mixed findings suggest that better designed studies may find a niche for some of these drugs. Amineptine was effective for withdrawal symptoms. 

It is perhaps not surprising that, even after taking into account pharmacokinetic differences between these drugs, the therapeutic doses of the SSRIs do not parallel their Ki for inhibition of 5-HT reuptake. For instance, citalopram is about a thousand times more selective than fluoxetine for inhibition of 5-HT uptake, and yet their clinically effective doses are similar. In short, not only is their selectivity for the 5-HT transporter in vitro a poor predictor of their efficacy in vivo but it has to be questioned whether any of these compounds actually work by blocking 5-HT uptake alone. 

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. 

A final experiment demonstrating the distinetion between the acute and neurotoxic effects of MDMA is shown in figure 12. In this case, the 5-HT uptake inhibitor fluoxetine was administered at various times after MDMA, with all animals being saerifieed 1 week later. The results are shown as a pereentage of eontrol eortieal 5-HT eoneentrations. Simultaneous administration of an uptake inhibitor with MDMA completely blocked the decrease in 5-HT concentrations measured 1 week later. However, administration of the inhibitor 3 hours after MDMA still resulted in complete protection from the neurotoxicity. Approximately 50 percent of the depletion could still be blocked 6 hours after MDMA by 12 hours, the administration of fluoxetine no longer had any effect. Blockade of the neurotoxicity by an uptake inhibitor 3 hours after MDMA clearly differentiates the acute and long-term effects of MDMA, since at this point the acute depletion of 5-HT is already at a maximum. The administration of fluoxetine to MDMA-treated animals... 

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). 

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