Psychopharmacology (Berl). 1990;102(2):273-7.
Behavioural analysis of the anorectic effects of fluoxetine and fenfluramine.

Willner P, McGuirk J, Phillips G, Muscat R.

Psychology Department, City of London Polytechnic, UK.

Two sets of experiments were carried out to compare the effects of fenfluramine and fluoxetine on consummatory and operant behaviour. In food-deprived rats allowed access to a 35% sucrose solution, an initial period of sucrose consumption was followed by a short period of grooming and exploratory behaviour, later superceded by resting. This "behavioural satiety sequence" was advanced by fluoxetine, but disrupted by dl-fenfluramine, which suppressed post-prandial resting, even at sub-anorectic doses. Fluoxetine also elicited resting behaviour following water drinking. However, this did not appear to be a non-specific sedative effect, since fluoxetine increased post-prandial grooming. In rats performing on random interval schedules of food reinforcement, fluoxetine caused proportionally greater decreases in responding on a reinforcement-lean schedule (RI-300s), as compared to a reinforcement-rich schedule (RI-7.5s); this effect is similar to that of a reduction in level of food deprivation. By contrast, fenfluramine reduced responding equally on both schedules. In both paradigms, the effects of fluoxetine were compatible with an increase in postprandial satiety, but the effects of fenfluramine were not.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2274610&dopt=Abstract fluoxetine




J Am Acad Child Adolesc Psychiatry. 1990 Jan;29(1):45-8.
Fluoxetine treatment of children and adolescents with Tourette's and obsessive compulsive disorders: preliminary clinical experience.

Riddle MA, Hardin MT, King R, Scahill L, Woolston JL.

Child Study Center, Yale University School of Medicine, New Haven, CT.

Fluoxetine hydrochloride is the first selective serotonin uptake inhibitor introduced commercially in the United States. This report describes preliminary clinical experience with fluoxetine in 10 children and adolescents, aged 8 to 15 years, with primary obsessive compulsive disorder (OCD) or Tourette's syndrome (TS) plus OCD. In general, fluoxetine, which was administered from 4 to 20 weeks at a dosage of 10 or 40 mg per day, was well tolerated. Adverse effects included behavioral agitation/activation in four patients and mild gastrointestinal symptoms in two patients. No abnormalities were noted in the seven children who had follow-up EKGs. Five of the 10 patients (50%) were considered responders; their obsessive-compulsive symptoms decreased substantially during treatment with fluoxetine. Responder rates were similar in the primary OCD (two of four, 50%) and TS + OCD (three of six, 50%) groups. In conclusion, short-term fluoxetine administration appears to be safe in children and adolescents. Placebo-controlled trials are needed to further assess the efficacy of fluoxetine.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2295577&dopt=Abstract fluoxetine




Pharmacol Biochem Behav. 1990 Jan;35(1):237-44.
Fluoxetine reduces intravenous cocaine self-administration in rats.

Carroll ME, Lac ST, Asencio M, Kragh R.

Psychiatry Department, University of Minnesota Medical School, Minneapolis 55455.

Rats self-administered intravenously delivered cocaine (0.2 mg/kg) under a fixed-ratio (FR) 4 schedule during 24-hr sessions. Water was freely available from both a drinkometer and a standard water bottle. After behavior had stabilized, the rats were injected with fluoxetine HCl at 10:00 a.m. and 4:00 p.m. for 5 consecutive days. Three groups of 5 rats each received a different dose of fluoxetine (2.5, 5 or 10 mg/kg) via the IV cannula. In three other groups of rats a glucose and saccharin solution (G + S) was substituted for water in the automatic drinking device and saline was substituted for cocaine. These three groups of rats received the same fluoxetine doses as the cocaine self-injecting groups. In two additional groups of 5 rats each, the cocaine dose was changed to 0.1 or 0.4 mg/kg, and 5 mg/kg fluoxetine injections were given. The two higher doses of fluoxetine (5 and 10 mg/kg) reduced cocaine infusions (0.2 mg/kg) by at least 50 percent on all 5 days of treatment, and cocaine infusions returned to baseline levels within 48 hr after fluoxetine treatments were terminated. Behavior maintained by the G + S solution was also reduced by the two higher fluoxetine doses; however, this reduction did not reliably occur until the last two days of fluoxetine administration. The G + S intakes returned to baseline levels within 24 hr after fluoxetine treatment. Fluoxetine also reduced cocaine infusions in the group of rats that received the lower unit dose of cocaine (0.1 mg/kg); however, it had almost no effect on behavior maintained by a higher cocaine dose (0.4 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2315363&dopt=Abstract fluoxetine




J Chromatogr. 1990 Jan 19;499:601-8.
Determination of fluoxetine and norfluoxetine by high-performance liquid chromatography.

Wong SH, Dellafera SS, Fernandes R, Kranzler H.

Department of Laboratory Medicine, University of Connecticut School of Medicine, Farmington 06032.

A high-performance liquid chromatographic assay was developed for a recently introduced atypical antidepressant, fluoxetine and its demethylated metabolite, norfluoxetine. Prior to analysis, aliquots of alkalinized plasma were extracted with n-hexane and isoamyl alcohol, followed by back-extraction with diluted phosphoric acid. These extracts were injected into a 10 microns, reversed-phase C18 column with phosphate and acetonitrile as the mobile phase and detection at 214 nm. Peak height ratios were linearly correlated up to 800 micrograms/l. Acceptable coefficients of variation were demonstrated for both within-run and day-to-day studies. Selected drugs were checked for interference. The assay was used to monitor nine patients receiving 20 to 80 mg of fluoxetine per day. Plasma concentrations of fluoxetine and norfluoxetine ranged from 37 to 301 micrograms/l and 29 to 326 micrograms/l respectively.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2324217&dopt=Abstract fluoxetine




Int Clin Psychopharmacol. 1990 Jan;5(1):41-8.
Clinical and experimental studies on fluoxetine: effects on serotonin uptake.

Butler J, Leonard BE.

Department of Pharmacology, University College, Galway, Ireland.

A decreased rate of uptake of serotonin (5HT) into platelets is recognized as a possible marker of the depressed state, being normalized only by effective antidepressant treatment. Fluoxetine is a novel antidepressant, with 5HT uptake inhibitory properties. In this study, treatment of depressed patients with fluoxetine for up to 6 months did not normalize the decreased platelet 5HT uptake rates associated with depression, although the patients showed a clinical recovery. The olfactory bulbectomized (OB) rat shows a characteristic hyperactivity in a stressful environment, which can be reversed only by chronic treatment with most antidepressants. OB rats have been found to exhibit a decreased rate of platelet 5HT uptake, similar to depressed patients, which is normalized by chronic antidepressant treatment. However, 3 weeks treatment with fluoxetine failed to reverse the hyperactivity of the OB rat and the decreased rates of uptake of 5HT. We also examined the rate of uptake of serotonin into the synaptosomes of the OB rats, in order to elucidate whether platelet 5HT uptake reflected central activity. Chronic fluoxetine treatment failed to normalize high affinity synaptosomal 5HT uptake in the OB rat. Fluoxetine, therefore, unlike most other antidepressants, does not normalize the decreased rates of platelet 5HT uptake in depressed patients on clinical recovery. OB rats also showed a deficit in their platelet and synaptosomal 5HT uptake rates, following 3 weeks treatment with fluoxetine.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2332607&dopt=Abstract fluoxetine




J Clin Psychiatry. 1990 Jun;51(6):222-5.
Adverse consequences of fluoxetine-MAOI combination therapy.

Feighner JP, Boyer WF, Tyler DL, Neborsky RJ.

Feighner Research Institute, La Mesa, Calif.

The authors describe two series of patients: 12 treated simultaneously with fluoxetine and a monoamine oxidase inhibitor and 6 patients started on treatment with an MAOI 10 days or more after stopping fluoxetine treatment. All patients had extremely refractory depression and were treated in open fashion before general knowledge was obtained of the side effects that may accompany the fluoxetine-MAOI combination. During the fluoxetine-MAOI trial, most patients continued to receive other psychotropic combinations that had been partially helpful. The use of fluoxetine and an MAOI, either together or in close succession, was accompanied by a very high incidence of adverse effects, especially the "serotonergic syndrome." This syndrome was characterized by mental status changes, such as hypomania and confusion, and physical symptoms, such as myoclonus, hypertension, tremor, and diarrhea. Because of the high incidence of side effects and the lack of definite efficacy, the concurrent use of fluoxetine and MAOIs should generally be avoided. The long half-lives of fluoxetine and norfluoxetine, as well as the prolonged metabolic effects of MAOIs, may also dispose patients to an interaction if one of the drugs is started soon after stopping the other.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2347858&dopt=Abstract fluoxetine




Psychosomatics. 1990 Summer;31(3):273-6.
Drug-drug interactions of fluoxetine with tricyclics.

von Ammon Cavanaugh S.

Department of Psychiatry, Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL 60612.

The drug-drug interactions with fluoxetine, a pure serotonergic reuptake blocker with a unique profile of side effects, have not been studied adequately. This preliminary report shows that desipramine and nortriptyline plasma levels are markedly increased at steady state (2 to 11 times) when coadministered with fluoxetine. This appears to be the result of the inhibition of the P450 enzyme system of the liver by fluoxetine, resulting in increased plasma levels of drugs metabolized by this system. Research must promptly address drug-drug interactions with fluoxetine since potentially all psychotropic drugs (except for lithium) and many medically indicated drugs could also have significant drug-drug interactions with fluoxetine.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2388981&dopt=Abstract fluoxetine




Brain Res Bull. 1988 Jul;21(1):43-6.
Fluoxetine increases the extracellular levels of serotonin in the nucleus accumbens.

Guan XM, McBride WJ.

Department of Psychiatry, Indiana University School of Medicine, Indianapolis 46233.

The effects of an IP injection of the monoamine uptake inhibitor fluoxetine on the extracellular concentration of serotonin (5-HT), dopamine (DA), 5-hydroxyindoleacetic acid (5-HIAA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the nucleus accumbens of awake and freely moving rats were examined using a push-pull perfusion technique. Baseline values of 5-HT, 5-HIAA, DA, DOPAC and HVA in the perfusates were approximately 0.07, 13, 0.8, 49 and 12 pmol/hr, respectively. The IP administration of 5 and 10 mg/kg fluoxetine dose-dependently elevated the amounts of 5-HT 3- and 13-fold, respectively, in the push-pull perfusate, with the maximum reached within one hour after drug administration. Moreover, 10 mg/kg fluoxetine also significantly decreased the levels of 5-HIAA in the perfusate as much as 50% within 2-3 hours. On the other hand, no significant effect of 5 or 10 mg/kg fluoxetine was observed on the contents of DA, DOPAC and HVA in the push-pull perfusates. The data indicate that fluoxetine, in accord with its role as a 5-HT uptake inhibitor, increases the physiologically active pool of 5-HT in the nucleus accumbens under in vivo conditions.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2464422&dopt=Abstract fluoxetine




Eur J Pharmacol. 1988 Sep 13;154(2):125-34.
Rapid down regulation of beta-adrenoceptors by co-administration of desipramine and fluoxetine.

Baron BM, Ogden AM, Siegel BW, Stegeman J, Ursillo RC, Dudley MW.

Merrell Dow Research Institute, Cincinnati, OH 45215.

Co-administration of desipramine and fluoxetine resulted in a 27% decline in cerebral cortical beta-adrenoceptor density after four days - a time point at which neither agent alone was effective. After 14 days, desipramine- and desipramine + fluoxetine-treated rats showed decreased receptor levels, with a greater decrement seen with the combined treatment. Fluoxetine, alone, had no affect on beta-adrenoceptor density at any time point examined. These effects are attributable to central serotonergic action since they were prevented by prior treatment with p-chlorophenylalanine. Cyproheptadine, a 5-HT2 antagonist, did not block these effects. Independent administration of fluoxetine and desipramine produced approximately 20% decrement in isoproterenol-stimulated cyclic AMP accumulation after four days of treatment. Co-administration of desipramine and fluoxetine resulted in a 35% decrement in cyclic AMP accumulation which was nearly additive with that produced by either drug alone. Consequently, the combination of a norepinephrine and serotonin uptake inhibitor may be an advantageous and rapid treatment for the alleviation of certain forms of depression.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2465908&dopt=Abstract fluoxetine