Drugs online research references
Pharmacol Toxicol. 2001 Feb;88(2):59-66.
The toxicity profile of a single dose of paroxetine: an alternative approach to acute toxicity testing in the rat.
Ryan PM, Kelly JP, Chambers PL, Leonard BE.
Department of Pharmacology, National University of Ireland, Galway.
In this study we have examined the effect of a single administration of the selective serotonin reuptake inhibitor, paroxetine (120-300 mg kg(-1), orally) in a recently developed rodent model of acute toxicity testing. Reduced body-weight, food consumption, water consumption and body temperature were observed in all paroxetine-treated groups, which were reversible within 7 days. Five days after administration, a dose-dependent increase in red blood cells, haemoglobin and haematocrit was observed with the 3 higher dose levels of paroxetine, which was significant in the 240 and 300 mg kg(-1) treatment groups (P < 0.05). Hyperactivity was apparent in the first 24 hr following treatment, as was evidence of the serotonin syndrome. When the animals were sacrificed (11 days after drug administration), an increase in liver weight was observed in the highest dose. These results are in agreement with those previously observed with paroxetine at the preclinical and clinical levels. They demonstrate that this rodent model, because of its multi-parameter nature, is a useful method for examining the consequences of a single high dose of an antidepressant drug.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11169163&dopt=Abstract
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J Pharmacol Exp Ther. 2001 Mar;296(3):987-95.
Modifications of the serotonergic system in mice lacking serotonin transporters: an in vivo electrophysiological study.
Gobbi G, Murphy DL, Lesch K, Blier P.
Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, Montreal, Canada.
The serotonin transporter (5-HTT) plays a key role in the regulation of serotonin (5-hydroxytryptamine, 5-HT) transmission in the pathophysiology and therapeutics of several psychiatric disorders. The mean spontaneous firing rate of midbrain dorsal raphe 5-HT neurons was recorded in chloral hydrate-anesthetized mice. The serotonin transporter (5-HTT), which plays a key role in the regulation of serotonin was significantly decreased in homozygous mice lacking the 5-HT transporter (5-HTT -/-) by 66% and in heterozygous (5-HTT +/-) mice by 36% compared with their normal littermates (5-HTT +/+). Systemic injection of the selective 5-HT(1A) receptor antagonist WAY 100635 enhanced 5-HT neuronal firing by 127% in 5-HT -/- mice, thus indicating an enhanced synaptic availability of 5-HT at inhibitory 5-HT(1A) receptors. Nevertheless, the cell body 5-HT(1A) autoreceptors were desensitized in both 5-HTT -/- and 5-HTT +/- mice. At the postsynaptic level, the recovery time (RT(50)) of the firing rate of hippocampus CA(3) pyramidal neurons following iontophoretic applications of 5-HT was significantly prolonged only in 5-HTT -/- mice. The selective 5-HT reuptake inhibitor paroxetine significantly prolonged the RT(50) in 5-HTT +/+ and 5-HTT +/- mice, without altering the maximal inhibitory effect of 5-HT. These neurons in 5-HTT -/- mice showed an attenuated response to the 5-HT(1A) agonist 8-hydroxy-2-diproplyaminotetralin, but not to 5-HT itself. These results establish that the lack of 5-HTT causes a prolonged recovery of firing activity following 5-HT applications. The genetic deletion of the 5-HTT plays a key role on 5-HT(1A) receptor adaptation: a desensitization at pre- and postsynaptic levels in 5-HTT -/- mice, but to a different extent, and only at the presynaptic level in the 5-HTT +/- group.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11181933&dopt=Abstract
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J Chromatogr B Biomed Sci Appl. 1999 Mar 19;724(2):393-8.
Determination of paroxetine in plasma by high-performance liquid chromatography for bioequivalence studies.
Lopez-Calull C, Dominguez N.
Hospital Sta. Creu i Sant Pau, Institut de Recerca, Barcelona, Spain.
A high-performance liquid chromatographic method is described for the determination of paroxetine in human plasma. Dibucaine was used as the internal standard. Paroxetine was isolated by solid phase extraction using a Bond-Elut C18 extraction column. Separation was obtained using a reversed-phase column under isocratic conditions with fluorescence detection. The sample volume was 500 microliters of plasma. The intra- and inter-assay accuracy and precision, determined as relative error and relative standard deviation, respectively, were less than 10%. The lower limit of quantitation, based on standards with acceptable relative error and relative standard deviation, was 10 ng ml-1. No endogenous compounds were found to interfere. The linearity was assessed in the range 5-100 ng ml-1. Stability of paroxetine during processing (autosampler) and in plasma was checked. This method proved suitable for bioequivalence studies following multiple doses in healthy volunteers.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10219683&dopt=Abstract
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