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Reflecting its potent inhibition of serotonin (5-HT) reuptake (accompanying paper), S33005 blocked spontaneous tail-flicks induced by parachloroamphetamine in rats. This action was mimicked by the 5-HT reuptake inhibitor, citalopram, and the 5-HT/norepinephrine (NE) reuptake inhibitor, venlafaxine, whereas the preferential NE reuptake inhibitor, reboxetine, was inactive. Consistent with its less potent interaction with NE transporters, higher doses of S33005 attenuated induction of hypothermia by reserpine, an action mimicked by reboxetine and venlafaxine, whereas citalopram was ineffective. In mice, S33005 reduced immobility in forced-swim and tail-suspension procedures. It also inhibited marble-burying behavior and suppressed aggressive behavior between resident and intruder animals. In rats, S33005 generalized to a discriminative stimulus elicited by citalopram and attenuated hypnotic-sedative actions of the alpha2-adrenoceptor agonist, S18616. For these parameters, S33005 was a more potent agent (median, 1.2 mg/kg, s.c.) than venlafaxine, citalopram, reboxetine, or the tricyclic agent, clomipramine. Even at markedly higher doses (40.0-80.0 mg/kg, s.c.), S33005 little affected motor behavior. S33005 (10.0 mg/kg, s.c.) also increased responses in a learned helplessness paradigm in rats, whereas venlafaxine was ineffective. Finally, in a rat chronic mild-stress model, S33005 dose- (2.5-40.0 mg/kg) and time- (2-5 weeks) dependently enhanced sucrose consumption. Venlafaxine was likewise active in this procedure. In conclusion, in line with its inhibition of 5-HT and (less potently) NE reuptake, S33005 is active in a broad range of models suggestive of antidepressant activity. It exerts its actions more potently than venlafaxine and clomipramine, and its overall profile is distinct from those of citalopram and reboxetine.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11454919&dopt=Abstract
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Ther Drug Monit. 1994 Feb;16(1):100-7.
A high-performance liquid chromatographic method for the simultaneous determination of venlafaxine and O-desmethylvenlafaxine in biological fluids.
Hicks DR, Wolaniuk D, Russell A, Cavanaugh N, Kraml M.
Drug Metabolism Division, Wyeth-Ayerst Research, Princeton, New Jersey 08540.
A rapid, accurate, and sensitive high-performance liquid chromatographic (HPLC) method for simultaneous determination of venlafaxine (V) and O-desmethylvenlafaxine (ODV) in plasma and urine has been developed. V and ODV are extracted from plasma using a liquid-liquid extraction procedure, chromatographed on a Supelcosil LC-8DB column, and quantitated by UV detection at 229 nm. Linearity was established over the range 10-500 ng/ml for V and 7.2-720 ng/ml for ODV using 1.0 ml of human, rat, dog, and mouse plasma. For urine, for both analytes, an analytical range 0.1-10.0 micrograms/ml was established. Accuracy of > +/- 10% about the theoretical mean was achieved for all matrices, with intra- and interday coefficients of variation for precision of < 10%. Endogenous components in plasma and/or urine or known metabolites of V do not interfere in the determination of the analytes. For both V and ODV a quantitation limit of 10 ng/ml for plasma was adequate for their estimation over a period of three half-lives, following administration of a pharmacologic dose in man, and the limit of 0.1 microgram/ml, for urine, can monitor excretion of as little as 0.5% of the dose.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8160247&dopt=Abstract
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J Chromatogr A. 2001 Jun 1;919(1):195-203.
Use of vancomycin silica stationary phase in packed capillary electrochromatography. II. Enantiomer separation of venlafaxine and O-desmethylvenlafaxine in human plasma.
Fanali S, Rudaz S, Veuthey JL, Desiderio C.
Istituto di Cromatografia, Consiglio Nazionale delle Ricerche, Area della Ricerca di Roma, Rome, Italy.
A capillary electrochromatography method, using vancomycin chiral stationary phase packed capillary, was optimized for the simultaneous chiral separation of the antidepressant drug venlafaxine and its main active metabolite O-desmethylvenlafaxine. Simultaneous baseline enantiomeric separation of the two compounds was obtained using a mobile phase composed of 100 mM ammonium acetate buffer pH 6/water/acetonitrile (5:5:90, v/v). The electrokinetic injection for sample introduction provided a limit of quantitation for both the compounds of 0.05 microg/ml racemate concentration suitable for the analysis of venlafaxine and metabolite in biological samples. The acetonitrile mobile phase concentration was found to modulate the analytes elution times, the enantiomeric resolution and the efficiency of the separation. The column was tested for repeatability and linearity showing RSD values (%) in the range of 0.13-0.24, 2.47-3.66 and 1.35-2.50 for migration time, sample/internal standard peak area ratio and enantiomeric resolution, respectively and correlation coefficients higher than 0.9990. The method was applied to the analysis of clinical samples of patients under depression therapy showing a stereoselective metabolism for venlafaxine.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11459304&dopt=Abstract
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