Drugs online research references
Med Biol. 1975 Aug;53(4):238-44.
Cardiovascular effects of amitriptyline, nortriptyline, protriptyline, and doxepin in conscious rabbits after subacute pretreatment with protriptyline.
Elonen E, Mattila MJ.
Conscious rabbits which had been permanently catheterized into their aortas and posterior caval veins, were injected daily with 10 mg/kg of protriptyline subcutaneously, divided in 3 doses. The blockade of the membrane pump in sympathetic nerve terminals by protriptyline was checked by pressor tests with noradrenaline (NA) and tyramine. In the presence of the membrane pump blockade 2.5 mg/kg of amitriptyline, nortriptyline, or protriptyline, or 3.0 mg/kg of doxepin was injected i.v. The antidepressants lowered blood pressure transiently and increased the heart rate, doxepin and amitriptyline being more effective than nortriptyline and protriptyline. Amitriptyline and doxepin provoked more severe cardiac arrhythmias on ECG than nortriptyline, and protriptyline caused no arrhythmias. Intravenous infusion of NA (11 mug/min) raised the blood pressure and lowered the heart rate. Injection of antidepressants during NA infusion resulted in more pronounced depressor and tachycardic effects than occurred without NA infusion. Major ECG changes were only slightly more apparent than without NA infusion. The rank order of toxicity of the antidepressants was the same. It is concluded that the NA potentiation by tricyclic antidepressants is not the main reason for their cardiotoxic effects.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1186320&dopt=Abstract
Neuropsychopharmacology. 1992 May;6(3):137-44.
Molecular structure and dynamics of the four 10-hydroxynortriptyline isomers.
Heimstad E, Edvardsen O, Dahl SG.
Department of Pharmacology, University of Tromso, Norway.
The three-dimensional structures, molecular conformations, and electrostatic potentials of the R-E-, S-E-, R-Z-, and S-Z-isomers of 10-hydroxynortriptyline were examined by computer graphics, molecular mechanical energy calculations, and molecular dynamics simulations in vacuo and in aqueous solution. Molecular models of the isomers, based on the structure of nortriptyline, were refined by energy minimization and used as starting points in the simulations. R-E- and S-Z-10-hydroxynortriptyline formed intramolecular hydrogen bonds between the side-chain nitrogen atom and the hydroxyl group during the simulations in vacuo, and had the side chain folded over the ring system in the minimum energy conformations. Intramolecular hydrogen bonding was not observed for R-Z- and S-E-10-hydroxynortriptyline, which had extended side chains in the minimum energy conformations and stronger negative molecular electrostatic potentials around the hydroxyl group than the R-E- and S-Z-isomers.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1599604&dopt=Abstract
Eur Neuropsychopharmacol. 1991 May;1(2):127-37.
Molecular structure and dynamics of tricyclic antidepressant drugs.
Heimstad E, Edvardsen O, Ferrin TE, Dahl SG.
Department of Pharmacology, Institute of Medical Biology, University of Tromso, Norway.
The molecular structure, electrostatic potentials and dynamics of imipramine, chlorimipramine, amitriptyline and nortriptyline were examined by computer graphics, molecular mechanical energy calculations and molecular dynamics simulations, using the AMBER all atom force field. Starting coordinates for amitriptyline and nortriptyline were generated by model building from the crystal structure of imipramine. The structures were refined by molecular mechanical energy minimization, and used as starting points for molecular dynamics simulations in vacuo and in aqueous solution. The simulations demonstrated considerable flexibility of the molecules, both in the side chain and in the ring system, where the angle between the phenyl rings varied between 90 degrees and 168 degrees. The most frequently observed conformations of imipramine, chlorimipramine and nortriptyline during the simulations had the side chain folded above one of the phenyl rings, while amitriptyline showed both folded and extended side chain conformations during the simulations. The results may provide increased understanding of the molecular recognition and specificity of tricyclic antidepressant drugs in interaction with neurotransmitter receptor molecules.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1821702&dopt=Abstract
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