Drugs online research references
Postgrad Med J. 1980;56 Suppl 1:94-8.
An external quality-control scheme for tricyclic antidepressants.
Jones S, Turner P.
Some hospital clinical pharmacology departments operate quality-control schemes to monitor the efficiency of their own and outside pharmacological laboratories in analysing specimens, to maintain or improve quality of performance and to compare the reliability of different methods. The Department of St. Bartholomew's Hospital, London, has been operating a quality-control scheme in which the results from some 18 or more laboratories in analysing the mixed tricyclic-antidepressant content of spiked sera were compared for reliability, six methods being used in all. The measures employed were the overall standard deviation and coefficient of variation, a small coefficient of variation indicating a good quality of performance. Sera contained either amitriptyline and nortriptyline, or imipramine and desipramine. The coefficients of variation were considerably smaller than those reported previously and were greater for external than internal laboratories, while laboratories where tricyclic antidepressants are assayed routinely had a low variation. The skill and experience of the analyst are therefore important. Although there is room for improvement in the scheme, it has already provided valuable objective measures of performance and emphasized the need for a self-critical approach.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7393835&dopt=Abstract
Clin Chem. 1977 Jun;23(6):1012-7.
Simultaneous measurement of secondary and tertiary tricyclic antidepressants by GC/MS chemical ionization mass fragmentography.
Wilson JM, Williamson LJ, Raisys VA.
We present a method for measuring seven commonly used tricyclic antidepressants in plasma. This method is suitable for monitoring therapeutic concentrations and for screening drug overdoses in cases where the identity of the abused tricyclic antidepressant may not be known. Drugs from alkalinized plasma are extracted into hexane in one step; two injections into the gas chromatograph/mass spectrometer follow. The tertiary amines (amitriptyline, doxepin, and imipramine) are analyzed by direct injection; the secondary amines (nortriptyline, desmethyldoxepin, desipramine, and protriptyline) are analyzed after derivitization with trifluoroacetic anhydride. Clomipramine and desmethyltrimipramine are suitable internal standards. Chemical ionization mass fragmentography, with methane as the reactant gas, is used. While maintaining specificity for these drugs, concentrations in human plasma ranging from 5 to 500 microng/liter can be measured. The coefficients of variation are about 4 to 11%.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=858192&dopt=Abstract
Mol Pharmacol. 1992 Nov;42(5):817-25.
8-hydroxy-2-(di-n-propylamino)tetralin-responsive 5-hydroxytryptamine4-like receptor expressed in bovine pulmonary artery smooth muscle cells.
Becker BN, Gettys TW, Middleton JP, Olsen CL, Albers FJ, Lee SL, Fanburg BL, Raymond JR.
Medical Service (Nephrology), Department of Veterans Affairs Medical Center, Durham, North Carolina 27705.
Bovine pulmonary artery smooth muscle (SM) cells express a novel 5-hydroxytryptamine (5-HT) (5-HT4-like) receptor coupled to cAMP accumulation. cAMP radioimmunoassay established the agonist and antagonist profiles of this receptor. 5-HT (EC50 = 91 +/- 33 nM) and 5-methoxytryptamine were equipotent at the SM cell 5-HT receptor and both were more potent than 5-carboxamidotryptamine. Other tryptamine derivatives were less potent but remained full agonists. These findings are consistent with previous reports regarding 5-HT4 and 5-HT4-like receptors in the central nervous system. The most potent antagonists were the antidepressant compounds nortriptyline (IC50 = 177 +/- 153 nM) and zimelidine (IC50 = 202 +/- 101 nM). The 5-HT3 and 5-HT4 antagonist 3-tropanyl-indole-3-carboxylate (ICS 205-930) was also a competitive antagonist at this 5-HT4-like receptor (pA2 = 6.3). Antagonist affinities differed slightly at the SM cell receptor, compared with other 5-HT4 and 5-HT4-like receptors in the central nervous system. Nonetheless, the SM cell 5-HT4-like receptor displayed the same differential antagonist potencies as reported for these other receptors (ICS 205-930 > MDL 72222 and mianserin > ketanserin). 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was the most potent agonist for this 5-HT4-like receptor (EC50 = 6.4 +/- 3.4 nM). 8-OH-DPAT-induced cAMP accumulation could be blocked by ICS 205-930 but not by the 5-HT1A antagonist 1-(2-methoxyphenyl)-4-[4-(2-pthalimido)butyl]piperazine hydrobromide, distinguishing the SM cell 5-HT receptor from 5-HT1A receptors. The mechanism of 5-HT-stimulated cAMP production was also investigated. First, GTP augmented basal and 5-HT-stimulated cAMP accumulation. Second, antisera to the carboxyl terminus of the alpha subunit of Gs, attenuated 5-HT-mediated adenylate cyclase activation. This established that 5-HT-stimulated cAMP accumulation in SM cells required GS. These findings suggest that SM cells express a novel 5-HT4-like receptor positively coupled to adenylate cyclase. An unexpected finding was that 8-OH-DPAT is a potent partial agonist. These studies suggest that there may be heterogeneity among 5-HT4-like receptors.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1331764&dopt=Abstract
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