Prozac
[Comparison of the effect of fluoxetine combined with hormone replacement therapy (HRT) and single HRT in treating menopausal depression]

[Article in Chinese]

Yu Q, Yin CX, Hui Y, Yu J, He FF, Wei J, Wu YY.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy Medical Sciences, Beijing 100730, China.

OBJECTIVE: To compare the treatment effects between fluoxetine plus hormone replacement therapy (HRT) and HRT alone on menopausal depression. METHODS: A total of 54 women with climacteric symptoms and depression were enrolled and randomly divided into two groups. The fluoxetine plus HRT group received fluoxetine (20 mg, qd, po) and cyclic use of conjugated estrogen 0.625 mg and medroxyprogesterone acetate 5 mg, while HRT group was assigned to receive cyclic use of conjugated estrogen 0.625 mg and medroxyprogesterone acetate 5 mg only. All subjects were interviewed and evaluated with Hamilton Depression score (HAMD) and Kupperman menopause index (KMI) at week 0, 1, 2, 3, 4, 6 and 8 of the treatment. RESULTS: There was no difference between two groups in HAMD and KMI before the trial (P > 0.05). HAMD scores at the 8th week in fluoxetine plus HRT group and HRT group were 3.0 +/- 2.3 and 11.2 +/- 5.8 respectively, being significantly different (P < 0.001). At the 6th week of treatment KMIs in fluoxetine plus HRT group and HRT group were 9 +/- 6 and 14 +/- 7 respectively, also significantly different (P < 0.05). The healing rates of fluoxetine plus HRT group and HRT group were 92% and 48% respectively, which were statistically different by Chi square test (P < 0.001). CONCLUSIONS: The effect of fluoxetine plus HRT on menopausal depression is significantly superior than that of HRT only and the difference becomes more obvious with treatment time. Both groups could ameliorate the climacteric symptoms with the effect of fluoxetine plus HRT more obvious.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15347469&dopt=Abstract fluoxetine Prozac



Prozac
Combined actions of zinc and fluoxetine on nicotinic acetylcholine receptors.

Garcia-Colunga J, Vazquez-Gomez E, Miledi R.

Instituto de Neurobiologia, Universidad Nacional Autonoma de Mexico, Campus Juriquilla, Queretaro, Mexico. garciac inb.unam.mx

Zinc and nicotinic acetylcholine receptors (nAChRs) seem to be associated with major depression, and some antidepressants, including fluoxetine (Prozac), antagonize nAChRs. Therefore, a study was made of the modulation of neuronal alpha4beta4 and muscle alpha1beta1gammadelta nAChRs, expressing in oocytes, by the combined action of zinc and fluoxetine. At a holding potential of -60 mV, 200 microM zinc increased by 361% the currents elicited by acetylcholine (ACh currents) for alpha4beta4 and by 182% for alpha1beta1gammadelta nAChRs. In contrast, 5 microM fluoxetine reduced the ACh currents to 31% for alpha4beta4 and to 45% for alpha1beta1gammadelta nAChRs. Additionally, fluoxetine reduced more the ACh currents in the presence of zinc: to 17% for alpha4beta4 and to 19% for alpha1beta1gammadelta nAChRs, and after washing out the fluoxetine the ACh current did not recover its zinc-potentiated value. Moreover, when ACh-activated nAChRs were exposed first to fluoxetine and then zinc was added, the potentiating effect of zinc was very small for muscle nAChRs and was nil for neuronal receptors. Thus, the inhibiting effect of fluoxetine prevails over the potentiating action of zinc. Finally, the effects of both zinc and fluoxetine were voltage independent, indicating that these substances interact outside the ion channel. As fluoxetine nullifies the effects of zinc, it appears that both substances interact in the same site. These results should help understand better the roles played by zinc, antidepressants, nAChRs and their combination in brain functions and in the treatment of depression.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15354177&dopt=Abstract fluoxetine Prozac



Prozac
Essentiality of central GABAergic neuroactive steroid allopregnanolone for anticonvulsant action of fluoxetine against pentylenetetrazole-induced seizures in mice.

Ugale RR, Mittal N, Hirani K, Chopde CT.

University Department of Pharmaceutical Sciences, Nagpur University Campus, Nagpur 440 033, Maharashtra, India.

Fluoxetine, a selective serotonin reuptake inhibitor, is known to increase the cortical content of allopregnanolone (ALLO) without altering the level of other neurosteroids. In contrast to the proconvulsant effect of many antidepressants, fluoxetine exhibits anticonvulsant effects. The present study was undertaken to examine the role of ALLO in the anticonvulsant action of fluoxetine against pentylenetetrazole (PTZ)-induced seizures in mice. Prior administration of GABA(A) receptor agonist muscimol or neurosteroid ALLO or progesterone, a precursor of ALLO or neurosteroidogenic drugs like FGIN 1-27, an agonist at the mitochondrial diazepam binding inhibitor receptor (MDR) or metyrapone, an 11beta-hydroxylase inhibitor, significantly potentiated the anticonvulsant effect of fluoxetine. In contrast, the effect of fluoxetine was counteracted by inhibition of the neurosteroid biosynthesis using drugs like 5alpha-reductase inhibitor, finasteride; 3beta-hydroxysteroid dehydrogenase inhibitor, trilostane; 3alpha-hydroxysteroid dehydrogenase inhibitor, indomethacin; MDR antagonist, PK 11195; or the GABA(A) receptor antagonist, bicuculline. Further, bilateral adrenalectomy had no significant effect on the anticonvulsant action of fluoxetine, suggesting negligible contribution from peripheral steroidogenesis. The anticonvulsant effect of fluoxetine was partially abolished in 5,7-DHT treated mice, indicating that the effect may also, in part, be dependent on serotonergic transmission. Thus, our data indicate that increased synthesis of ALLO in CNS is a major factor that ultimately leads to anticonvulsant effects of fluoxetine against PTZ-induced seizures.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15364024&dopt=Abstract fluoxetine Prozac



Prozac
[Idendification of the drugs in the mixture using thin-layer chromatography in sudden poisoning cases]

[Article in Lithuanian]

Kazlauskiene D, Vainauskas P, Rakauskaite D.

Department of Analytical and Toxicological Chemistry, Institute of Pharmacy, Kaunas University of Medicine, A. Mickeviciaus 9, 3000 Kaunas, Lithuania. daivakazlauskiene centras.lt

The problem of acute intoxication has become very urgent now due to a great number of various chemical preparations accumulated during the last decades in the environment. Intoxications with psychotropic drugs and their mixtures form the significant part of the intoxications; there is an increasing tendency of intoxication with several preparations at a time. Amitriptyline and codeine are the preparations, which more frequently can cause intoxication. Fluoxetine is one of the newest and often used antidepressants. Under certain circumstances, like overdose, using all preparations together, long term using or using for suicide, these preparations can be even a cause of death. In such cases amitriptyline, fluoxetine and codeine become the objects of chemical-toxicological analysis. The possibility of the separation and identification of amitriptyline, fluoxetine and codeine in the mixture using thin-layer chromatography was established. Dragendorf reagent, modified by Munje, is most suitable for the spray-distinct of the chromatographic plates for all three substances. Amitriptyline research limit, using this developer, is 0.4 micro g, fluoxetine - 1.6 micro g, codeine - 0.8 micro g. Most acceptable for separation the components of the mixture are 5 mobile phases: 1. Diethyl acetate-methanol-ammonium hydroxide (concentrated solution) (85:10:5). Amitriptyline, fluoxetine and codeine R(f) medium values respectively are 0.94; 0.63; 0.51. 2. Buthylacetate-methanol-ammonium hydroxide (concentrated solution) (85:10:5). Amitriptyline, fluoxetine and codeine R(f) medium values respectively are 0.65; 0.24; 0.15. 3. Cyclohexane-diethyl acetate-diethyl amine (70:15:15). Amitriptyline, fluoxetine and codeine R(f) medium values respectively are 0.93; 0.75; 0.37. 4. Cyclohexane-buthylacetate-diethyl amine (70:15:15). Amitriptyline, fluoxetine and codeine R(f) medium values respectively are 0.92; 0.51; 0.25. 5. Acetone-1,4-dioxane-ammonium hydroxide (concentrated solution) (30:68:2). Amitriptyline, fluoxetine and codeine R(f) medium values respectively are 0.82; 0.62; 0.42. Recommended methodology for the separation and identification of amitriptyline, fluoxetine and codeine in the mixture using thin-layer chromatography is statistically reliable: when confidence level is 0.95, relative error is less than 0.05; standard deviation is from 0.007 to 0.03. Recommended methodology suits for mixture, extracted from biological liquids, components separation and identification.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14617874&dopt=Abstract fluoxetine Prozac



Prozac
Long-term effects of fluoxetine or vehicle administration during pregnancy on behavioral outcomes in guinea pig offspring.

Vartazarmian R, Malik S, Baker GB, Boksa P.

Department of Psychiatry, Douglas Hospital Research Center, McGill University, 6875 LaSalle Boulevard, Verdun, QC, Canada, H4H 1R3, patricia.boksa mcgill.ca.

RATIONALE: Assessment of the benefits versus risks associated with antidepressant use during pregnancy must include an analysis of possible drug effects on fetal development. Human studies indicate that prenatal fluoxetine exposure is associated with adverse neonatal outcomes. Animal modeling may provide useful information concerning possible long-term effects of prenatal fluoxetine exposure. Limitations in previous such studies using rat models may be overcome using a guinea pig model in which fluoxetine is delivered by osmotic pump throughout pregnancy.METHODS: Initial experiments measured the half-life of fluoxetine and dosing required to achieve human therapeutic blood levels in the guinea pig. In subsequent experiments, guinea pigs received fluoxetine or vehicle via osmotic pump or no treatment throughout pregnancy. Outcome measures included: pregnancy characteristics, weight gain, and, in offspring as adults, pain threshold, acoustic startle responses and prepulse inhibition.RESULTS: There was no effect of treatment group on gestation length, number of live-births or still-births, maternal or offspring weight gain, and acoustic startle responses. In adult offspring, pain threshold was decreased by vehicle treatment during gestation. Prenatal fluoxetine increased pain threshold, relative to vehicle controls. Prepulse inhibition of startle was increased in adult offspring treated prenatally with either vehicle or fluoxetine compared to no treatment.CONCLUSIONS: The guinea pig provides a practicable and clinically relevant model of prenatal fluoxetine exposure. Adult guinea pigs exposed to fluoxetine prenatally showed increased thermal pain thresholds but no change in prepulse inhibition, indicating selective long-term effects of prenatal fluoxetine on serotonin-modulated behaviors. Further studies on long-term effects of prenatal fluoxetine on nociception are warranted.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15365684&dopt=Abstract fluoxetine Prozac



Prozac
Listening to generic Prozac: winners, losers, and sideliners.

Druss BG, Marcus SC, Olfson M, Pincus HA.

Mental Health, Emory University in Atlanta, USA. bdruss emory.edu

This study tracks the diffusion of generic fluoxetine after its release in August 2001 within the largest U.S. pharmacy benefit manager (PBM). Within two weeks of the generic's release, prescriptions exceeded those of brand-name Prozac. The main winners proved to be Barr Laboratories, the first entrant to the generic market; large purchasers, who reaped substantial cost savings after Barr's period of exclusivity expired; and the PBM. The major loser was Eli Lilly, the manufacturer of Prozac. Consumers and makers of other antidepressants largely remained on the sidelines, with surprisingly little short-term impact evident from Prozac's patent expiration.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15371387&dopt=Abstract fluoxetine Prozac



Prozac
Acute and chronic toxicity of five selective serotonin reuptake inhibitors in Ceriodaphnia dubia.

Henry TB, Kwon JW, Armbrust KL, Black MC.

Department of Environmental Health Science, University of Georgia, Athens, Georgia 30602, USA. thenry uga.edu

Contamination of surface waters by pharmaceutical chemicals has raised concern among environmental scientists because of the potential for negative effects on aquatic organisms. Of particular importance are pharmaceutical compounds that affect the nervous or endocrine systems because effects on aquatic organisms are possible at low environmental concentrations. Selective serotonin reuptake inhibitors (SSRIs) are drugs used to treat clinical depression in humans, and have been detected in low concentrations in surface waters. In this investigation, the acute and chronic toxicity of five SSRIs (fluoxetine, Prozac; fluvoxamine, Luvox; paroxetine, Paxil; citalopram, Celexa; and sertraline, Zoloft) were evaluated in the daphnid Ceriodaphnia dubia. For each SSRI, the 48-h median lethal concentration (LC50) was determined in three static tests with neonate C. dubia, and chronic (8-d) tests were conducted to determine no-observable-effect concentrations (NOEC) and lowest-observable-effect concentrations (LOEC) for reproduction endpoints. The 48-h LC50 for the SSRIs ranged from 0.12 to 3.90 mg/L and the order of toxicity of the compounds was (lowest to highest): Citalopram, fluvoxamine, paroxetine, fluoxetine, sertraline. Mortality data for the 8-d chronic tests were similar to the 48-h acute data. The SSRIs negatively affected C. dubia reproduction by reducing the number of neonates per female, and for some SSRIs, by reducing the number of broods per female. For sertraline, the most toxic SSRI, the LOEC for the number of neonates per female was 0.045 mg/L and the NOEC was 0.009 mg/L. Results indicate that SSRIs can impact survival and reproduction of C. dubia; however, only at concentrations that are considerably higher than those expected in the environment.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15379001&dopt=Abstract fluoxetine Prozac



Prozac
Gestational treatment with cocaine and fluoxetine alters oxytocin receptor number and binding affinity in lactating rat dams.

Johns JM, Lubin DA, Walker CH, Joyner P, Middleton C, Hofler V, McMurray M.

Department of Psychiatry, The University of North Carolina at Chapel Hill, 424 Taylor Hall, CB #7096, Chapel Hill, NC 27599-7096, USA. jjohns med.unc.edu

Cocaine administered chronically throughout gestation has been correlated with deficits in maternal behavior, increased maternal aggressive behavior and decreased oxytocin levels in rats. In addition to its effects on oxytocin levels, cocaine is a potent serotonergic, dopaminergic and noradrenergic reuptake inhibitor. Alterations in the dopaminergic and serotonergic systems have been suggested as possibly having a role in cocaine-induced maternal aggression. This study was in part, an attempt to understand some of the mechanisms by which cocaine increases postpartum aggression, particularly as they relate to changes in the oxytocin system. Oxytocin receptor number and binding affinity in the medial preoptic area of the hypothalamus, ventral tegmental area, hippocampus and amygdala were determined for lactating rat dams on postpartum day 6 (PPD 6) that were gestationally treated with cocaine, fluoxetine, saline or an amfonelic acid/fluoxetine drug combination. Cocaine and fluoxetine treatment both resulted in a significant up-regulation of oxytocin receptor number and lower receptor affinity in the amygdala of lactating rat dams compared to saline controls and the amfonelic acid/fluoxetine combination treatment group. Cocaine treatment also resulted in a significant down-regulation of oxytocin receptors in the medial preoptic area and both cocaine and fluoxetine treated dams had the highest affinity for oxytocin receptors in this brain region. Results of the present study support previous data indicating that alterations in oxytocinergic and perhaps serotonergic system dynamics in the amygdala may play a role in cocaine-induced postpartum aggression.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15380831&dopt=Abstract fluoxetine Prozac