Pharmacological characterization of BNMPA (alpha-benzyl-N-methylphenethylamine), an impurity of illicit methamphetamine synthesis. Fluoxetine-elicited changes in brain neurosteroid content measured by negative ion mass fragmentography. Selective serotonin reuptake inhibitors (SSRIs) in the treatment of elderly depressed patients: a qualitative analysis of the literature on their efficacy and side-effects. Rx drugs

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Eur J Pharmacol. 1996 Sep 12;311(2-3):133-9.
Pharmacological characterization of BNMPA (alpha-benzyl-N-methylphenethylamine), an impurity of illicit methamphetamine synthesis.

Moore KA, Mirshahi T, Compton DR, Poklis A, Woodward JJ.

Department of Pathology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0165, USA.

alpha-Benzyl-N-methylphenethylamine (BNMPA), an impurity of illicit methamphetamine synthesis, has previously been reported to produce convulsions in mice without affecting spontaneous locomotor activity or altering methamphetamine-induced increases in spontaneous activity. In this study the in vitro effects of BNMPA on a variety of neuronal receptor types was determined to better characterize the pharmacological actions of this novel compound. BNMPA and N-demethyl-BNMPA fully displaced the dopamine transporter selective ligand [3H]CFT (2-beta-carbomethoxy-3-beta-(4-fluorophenyl)tropane) from rat striatal membranes with Ki values (mean +/- S.E.M) of 6.05 microM +/- 0.15 and 8.73 microM +/- 1.66, respectively. BNMPA also inhibited [3H]dopamine uptake into striatal synaptosomes with an IC50 value of 5.1 +/- 1.4 microM. The basal efflux of [3H]dopamine from striatal slices was slightly enhanced by BNMPA only at concentrations > or = 100 microM. BNMPA had no effect on [3H]norepinephrine efflux from hippocampal slices. BNMPA displaced tritiated paroxetine and prazosin binding from rat cortical membranes with Ki values of 14.5 microM and 11.7 microM respectively. In electrophysiological studies, BNMPA (100 microM) had no significant effects on either GABAA Cl- currents in cultured neurons or non-NMDA glutamate receptors expressed in oocytes. However, BNMPA significantly inhibited NMDA-stimulated currents in oocytes expressing the NR1/2A or NR1/2C receptor subunit combinations (IC50 values = 24.6 +/- 1.8 and 24.0 +/- 1.5 microM, respectively). This inhibition was rapid, reversible and voltage-dependent. These results indicate that BNMPA has multiple sites of action in the CNS that could be important in modulating a variety of behavioral effects upon exposure to this synthetic byproduct of illicit methamphetamine synthesis.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8891593&dopt=Abstract

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Proc Natl Acad Sci U S A. 1996 Oct 29;93(22):12599-604.
Fluoxetine-elicited changes in brain neurosteroid content measured by negative ion mass fragmentography.

Uzunov DP, Cooper TB, Costa E, Guidotti A.

Department of Psychiatry, University of Illinois at Chicago 60612, USA.

Fluoxetine administered intraperitoneally to sham-operated or adrenalectomized/castrated (ADX/CX) male rats dose-dependently (2.9-58 mumol/kg i.p.) increased the brain content of the neurosteroid 3 alpha-hydroxy-5 alpha-pregnan-20-one (allopregnanolone, 3 alpha, 5 alpha-TH PROG). The increase of brain 3 alpha, 5 alpha-TH PROG content elicited by 58 mumol/kg fluoxetine lasted more than 2 hr and the range of its extent was comparable in sham-operated (approximately 3-10 pmol/g) and ADX/CX rats (2-9 pmol/g) and was associated with a decrease (from 2.8 to 1.1 pmol/g) in the 5 alpha-pregnan-3,20-dione (5 alpha-dihydroprogesterone, 5 alpha-DH PROG) content. The pregnenolone, progesterone, and dehydroepiandrosterone content failed to change in rats receiving fluoxetine. The extent of 3 alpha, 5 alpha-TH PROG accumulation elicited by fluoxetine treatment differed in various brain regions, with the highest increase occurring in the olfactory bulb. Importantly, fluoxetine failed to change the 3 alpha, 5 alpha-TH PROG levels in plasma, which in ADX/CX rats were at least two orders of magnitude lower than in the brain. Two other serotonin re-uptake inhibitors, paroxetine and imipramine, in doses equipotent to those of fluoxetine in inhibiting brain serotonin uptake, were either significantly less potent than fluoxetine (paroxetine) or failed to increase (imipramine) 3 alpha, 5 alpha-TH PROG brain content. The addition of 10 microM of 5 alpha-DH PROG to brain slices of ADX/CX rats preincubated with fluoxetine (10 microM, 15 min) elicited an accumulation of 3 alpha, 5 alpha-TH PROG greater than in slices preincubated with vehicle. A fluoxetine stimulation of brain 3 alpha, 5 alpha-TH PROG biosynthesis might be operative in the anxiolytic and antidysphoric actions of this drug.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8901628&dopt=Abstract

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Int Clin Psychopharmacol. 1996 Sep;11(3):165-75.
Selective serotonin reuptake inhibitors (SSRIs) in the treatment of elderly depressed patients: a qualitative analysis of the literature on their efficacy and side-effects.

Menting JE, Honig A, Verhey FR, Hartmans M, Rozendaal N, de Vet HC, van Praag HM.

Department of Psychiatry and Neuropsychology, University of Limburg Maastricht, The Netherlands.

A qualitative analysis of studies on the efficacy and side-effects of selective serotonin reuptake inhibitors (SSRIs) for the treatment of elderly people with depression is presented. Only placebo-controlled or comparison studies of SSRI versus other antidepressants were included. The description and methodological quality of the analysed studies were important criteria in the outcome of the analysis. Quality was assessed by means of a blinded review approach. After excluding duplicate publications, 16 studies were analysed, of which six turned out to be of good quality. The results indicated that at the end of the treatment periods (4-8 weeks) all antidepressants were equally effective. Side-effects occurred less frequently with SSRIs than with tricyclics (TCAs), and different side-effect profiles were found. Significantly fewer SSRI-treated patients than TCA-treated patients dropped out both overall and due to side-effects.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8923095&dopt=Abstract

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