Drugs online research references
Eur J Pharmacol. 1979 Aug 1;57(2-3):219-25.
Effect of various antidepressant drugs on the spontaneous firing rate of locus coeruleus and dorsal raphe neurons of the rat.
Scuvee-Moreau JJ, Dresse AE.
The spontaneous firing rate of the noradrenergic neurons of the locus coeruleus and of the serotonergic neurons of the dorsal raphe was recorded with extracellular microelectrodes in chloral hydrate-anesthetized rats. A quantitative comparison of the effect of five tricyclic antidepressants, of tranylcypromine and of mianserin on the spontaneous activity of these two types of cells was performed. All drugs tested, except mianserin reduced the frequency of discharge of the noradrenergic neurons. Intravenous perfusion of the drugs allowed the doses required for inhibition of firing to 50% of the baseline rate (ID50) to be determined. Secondary aminated antidepressants (desipramine and nortriptyline) were more potent inhibitors than their tertiary aminated analogues (imipramine, chlorimipramine and amitriptyline). All drugs tested, except desipramine decreased the rate of firing of the serotonergic cells. In this case, the tertiary aminated antidepressants were much more potent than their secondary analogues. Mianserin was only active at very high doses. These results are in good agreement with the relative potencies of the tricyclic antidepressants for blocking the uptake of noradrenaline and serotonin into central and peripheral neurons.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=488160&dopt=Abstract
J Pharm Pharmacol. 1978 Sep;30(9):547-53.
The use of 13C-nmr spectroscopy for the detection and identification of metabolites of carbon-13 labelled amitriptyline.
Hawkins DR, Midgley I.
The antidepressant drug amitriptyline and two of its metabolites, nortriptyline and desmethylnortriptyline, each containing two 13C atoms, have been used to determine the sensitivity and selectivity of 13C-nmr spectroscopy for the detection of unchanged amitriptyline and N-desmethyl metabolites in the urine of animals dosed orally with the labelled drug. The resonance signals from the 13C atoms detected in the 13C-nmr spectrum of entire extract from a control 12 h rat urine sample to which 1 mg of each labelled compound had been added were easily detected, using an instrument accumulation time of 1 h. The 13C-nmr spectrum of an extract of hydrolysed urine from a dog that had received an oral dose of [13C2]amitriptyline (30mg) exhibited signals that could be assigned to metabolites resulting from N-dealkylation and N-oxidation, as well as those bearing the intact amitriptyline side-chain. These assignments were confirmed by analysis of the same extract by g.c.--ms and h.p.l.c.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=29092&dopt=Abstract
J Chromatogr. 1984 Jan 13;305(1):73-82.
Gas chromatographic--mass spectrometric determination of amitriptyline and its major metabolites in human serum.
Ishida R, Ozaki T, Uchida H, Irikura T.
A gas chromatographic--electron-impact ionization mass spectrometric method has been developed for the determination of amitriptyline (AMT) and its metabolites, nortriptyline (NT), 10-hydroxyamitriptyline (10-OH-AMT) and 10-hydroxynortriptyline (10-OH-NT) in human serum. The lower limit of detection was 2 ng/ml for all compounds except 5 ng/ml for 10-OH-NT. The calibration curves for AMT and 10-OH-AMT were linear up to 100 ng/ml, and up to 200 ng/ml for NT and 10-OH-NT. The accuracy of the assay in terms of coefficient of variation was less than 7%. The extraction efficiency was almost quantitative for all compounds except 60% for 10-OH-NT. Using this method, human serum samples which had been collected after oral administration of a single 50-mg dose of AMT were analyzed. Ratios of the conjugation of each metabolite were estimated, including AMT.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6707156&dopt=Abstract
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