Drugs online research references
Biomed Chromatogr. 1996 Nov-Dec;10(6):351-4.
HPLC of sertraline and norsertraline in plasma or serum.
Patel J, Spencer EP, Flanagan RJ.
Poisons Unit, Guy's and St Thomas' Hospital Trust, London, UK.
A simple method for the measurement of sertraline and norsertraline in plasma or serum suitable for use in single-dose pharmacokinetic studies has been developed. Internal standard solution, aqueous fenethazine (10 mg/L) (20 microL), and Tris buffer (2 mol/L), pH 10.6) (100 microL) were added to plasma (200 microL). Sertraline, norsertraline and the internal standard were extracted into methyl tert-butyl ether (200 microL) by mixing (30 s) and centrifugation (11,000 r.p.m., 4 min). A portion (100 microL) of the extract was injected onto a Spherisorb S5SCX HPLC column (150 x 4.6 mm i.d.) which was eluted with methanol:water (19 + 1) containing ammonium perchlorate (40 mmol/L), final pH 7.0. Detection was by UV monitoring (215 nm). The concentration of each analyte in each sample was calculated from the calibration graph (peak-height ratio of analyte to that of the internal standard against concentration) obtained after analysis of plasma samples containing known amounts of sertraline and norsertraline. The limit of accurate measurement of the assay was 10 micrograms/L) sertraline and 20 micrograms/L) norsertraline.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8949919&dopt=Abstract
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Pharmacol Biochem Behav. 1996 Nov;55(3):387-96.
The stimulatory and inhibitory components of cocaine's actions on the 5-HTP-induced 5-HT2A receptor response.
Darmani NA, Reeves SL.
Department of Pharmacology, Kirksville College of Osteopathic Medicine, MO 63501, USA.
Previously we have shown that cocaine attenuates the 5-HT2A receptor-mediated head-twitch response (HTR) in mice produced by the 5-HT2A/C direct agonist (+/-)-1 (2.5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). This inhibition appears to be due to cocaine-induced indirect stimulation of the inhibitory serotonergic 5-HT1A and noradrenergic alpha 2 receptors via the inhibition of reuptake of synaptic serotonin (5-HT) and norepinephrine (NE), respectively. In the present study, we investigated the effects of cocaine, its phenyltropane analogue WIN 35428, and the selective 5-HT (sertraline). NE (nisoxetine) and dopamine (DA) (GBR 12935) reuptake inhibitors on the 5-hydroxytryptophan (5-HTP)-induced HTR. We utilized two experimental protocols where cocaine or the cited drugs were administered either after (protocol 1) or prior (protocol 2) to 5-HTP injection. Cocaine in both protocols produced a dose-dependent enhancement in the 5-HTP-induced HTR (ED50 4.68 +/- 1.21 and 3.55 +/- 1.31, respectively). Sertraline was more potent (ED50 2.64 +/- 1.1 and 2.1 +/- 1.54, respectively) in enhancing the induced behavior and dose by dose produced greater (3 to 10 times) HTRs than cocaine. On the other hand, nisoxetine dose dependently and completely attenuated the induced behavior (ID50 3.33 +/- 1.32 and 1.72 +/- 1.34, respectively), whereas GBR 12935 only at high doses (ID50 15.34 +/- 1.52 and 11.91 +/- 1.3, respectively) decreased the induced response. The inability of cocaine to induce as many HTRs as sertraline appears to lie in its ability to also indirectly stimulate the inhibitory 5-HT1A and alpha 2 receptors because the stimulant caused greater enhancement in the 5-HTP-induced HTRs in the presence of their corresponding antagonists [S(-)-UH 301 and yohimbine, respectively]. WIN 35428 was more potent (ED50 2.87 +/- 1.3 and 1.79 +/- 1.1 for protocols 1 and 2, respectively) in stimulating the 5-HTP-induced HTR and produced a bell-shaped dose-response curve. The results indicate that cocaine enhances the 5-HTP-induced HTR via the inhibition of synaptic 5-HT reuptake. The stimulant also simultaneously attenuates the induced behavior by indirect simulation of the serotonergic 5-HT1A and noradrenergic alpha 2 receptors via inhibition of reuptake of the corresponding monoamines.
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Br J Clin Pharmacol. 1996 Dec;42(6):757-63.
A comparison of the post-marketing safety of four selective serotonin re-uptake inhibitors including the investigation of symptoms occurring on withdrawal.
Price JS, Waller PC, Wood SM, MacKay AV.
Post-Licensing Division, Medicines Control Agency, Vauxhall, London, UK.
1. We have addressed the question of whether there is a 'serotonin withdrawal syndrome' by analysis of spontaneous reports of suspected adverse drug reactions (ADRs) associated with four SSRIs. A comparison of the post-marketing safety profiles of the four SSRIs has also been made. 2. The UK database of ADRs was examined for reactions associated with fluoxetine, fluvoxamine, paroxetine and sertraline. The safety profiles of the four SSRIs were similar. However, withdrawal reactions with paroxetine constitute a greater proportion of reports (5.1%) than with the other SSRIs (0.06-0.9%). They have been reported more often with paroxetine (0.3 reports per thousand prescriptions) than with sertraline and fluvoxamine (0.03), and least often with fluoxetine (0.002). 3. Descriptions of withdrawal reactions received and further details of 217 reports of withdrawal reaction with paroxetine obtained by mailing a questionnaire to the reporting doctor were examined. Withdrawal symptoms were diverse but most commonly comprised dizziness, paraesthesia, tremor, anxiety, nausea and palpitation. They usually occurred after 2 days and lasted for an average of 10 days. There was no evidence of a physical drug dependency syndrome. 4. Symptoms different from the previous depressive illness occur after discontinuing an SSRI, and are reported most often with paroxetine. Paroxetine is the most pharmacologically specific of the SSRIs, but it is not clear whether the reactions constitute a 'serotonin withdrawal syndrome'.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8971432&dopt=Abstract
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