Drugs online research references
Xenobiotica. 1988 Jan;18(1):123-9.
Pharmacokinetic and pharmacodynamic modelling of the alpha adrenoceptor antagonist doxazosin.
Meredith PA, Elliott HL, Kelman AW, Vincent J, Reid JL.
University of Glasgow, Department of Materia Medica, Stobhill General Hospital, UK.
1. The pharmacokinetic and pharmacodynamic profiles of intravenous and oral doxazosin were investigated in 6 normotensive volunteers. 2. The pharmacokinetics of i.v. and oral doxazosin were fitted simultaneously and independently. The parameters derived were in good agreement with a mean elimination half-life of 539 +/- 75 min, bioavailability of 0.65 +/- 0.11 and clearance of 140 +/- 26 ml/min. 3. Pharmacokinetic-pharmacodynamic modelling indicated that the sensitivities to oral and i.v. doxazosin in individual subjects were in good agreement. 4. Based on these findings it is unlikely that doxazosin metabolites contribute significantly to the pharmacodynamic profile of doxazosin.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2895548&dopt=Abstract
J Med Chem. 1988 May;31(5):1036-9.
1,3-Diamino-6,7-dimethoxyisoquinoline derivatives as potential alpha 1-adrenoceptor antagonists.
Bordner J, Campbell SF, Palmer MJ, Tute MS.
Department of Discovery Chemistry, Pfizer Central Research, Sandwich, Kent, United Kingdom.
Treatment of 2-methyl-4,5-dimethoxybenzonitrile (3) with LDA followed by reaction with an N,N-disubstituted cyanamide provided a series of 1,3-diamino-6,7-dimethoxyisoquinolines (2), which were evaluated for alpha-adrenoceptor binding affinity and antihypertensive activity. 1-Amino-3-(dimethylamino)-6,7-dimethoxyisoquinoline (4) showed no significant affinity (Ki much greater than 10(-6) M) for alpha 1-adrenoceptors, while the corresponding 3-(2-furoylpiperazin-1-yl) analogue (8; Ki = 1.6 X 10(-7) M) was some 1000-fold less potent than prazosin. pKa data showed that N-2 protonation (34%) of 4 (pKa = 7.1) would occur at physiological pH, in agreement with X-ray crystallographic analysis of 8.HCl. Comparison of positive charge distribution following protonation of 4 with the corresponding quinoline and quinazoline cations confirmed N-1 protonation is required for these heterocyclic nuclei to bind efficiently to the alpha 1-adrenoceptor. Computer-assisted comparison of the X-ray structures of 8 and prazosin suggested that the 4.0 kcal/mol difference in alpha 1-adrenoceptor binding energies was largely due to salt-bridge formation (ca. 3.0 kcal/mol) between the protonated quinazoline and the receptor protein. None of the isoquinolines (2) proved to be effective antihypertensive agents in rats even when administered at relatively high doses (10 mg/kg). These results support the hypothesis that the antihypertensive activity of prazosin, doxazosin, and related derivatives derives solely from alpha 1-adrenoceptor blockade.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2896246&dopt=Abstract
Am J Physiol. 1988 Nov;255(5 Pt 2):H1000-3.
alpha-Adrenoceptors and cold-induced vasoconstriction in human finger skin.
Ekenvall L, Lindblad LE, Norbeck O, Etzell BM.
Department of Occupational Medicine, Karolinska Sjukhuset, Stockholm, Sweden.
Experiments were designed to determine how cold-induced vasoconstriction is mediated in superficial vessels of human finger skin. alpha-Adrenoceptor antagonists were administered into the finger skin by iontophoresis, and local cooling was applied by a laser-Doppler probe supplied with Peltier elements. Cold-induced vasoconstriction was abolished after administration of the alpha 2-adrenoceptor antagonist rauwolscine but not after the alpha 1-adrenoceptor antagonist doxazosin. The results indicate that vasoconstriction on local cooling in human finger skin is mainly mediated by adrenoceptors of the alpha 2-subtype.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2903677&dopt=Abstract
online pharmacies ||
Hair Million herbal formula for hair loss and hair growth ||
Amoxicillin ||
Tramadol ||
Paxil ||
Rx Drugs USA, Prescription Drugs Online Pharmacy ||
Zithromax ||
online pharmacy ||
Antibiotics and prescription medications online literature ||
Antibiotics