Drugs online research references
Pain. 1985 Apr;21(4):329-37.
Potentiation of morphine antinociception by monoamine reuptake inhibitors in the rat spinal cord.
Taiwo YO, Fabian A, Pazoles CJ, Fields HL.
Potentiation of the antinociceptive effects of morphine by the tricyclic antidepressants was assayed in awake restrained rats using the tail-flick test. Intrathecally administered amitriptyline, desipramine or sertraline at doses that had no effect themselves (25-30 micrograms) potentiated a subthreshold parenteral dose of morphine (0.5 mg/kg). The morphine potentiating effect of amitriptyline was prevented by prior administration of parachlorophenylalanine (PCPA). This effect of PCPA was not restored by 5-hydroxytryptophan (5-HTP) but was restored when the animals were left for 14 days to replete. The morphine potentiating effects of amitriptyline, desipramine and sertraline were blocked by intrathecal administration of low doses of the serotonin antagonist methysergide and the alpha-adrenergic antagonists yohimbine and phentolamine but not by the beta-adrenergic antagonist propranolol. The results are consistent with the hypothesis that the potentiation of morphine's antinociceptive effect by tricyclic antidepressants depends on activation of both spinopetal serotonin and adrenergic neurons.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=4000684&dopt=Abstract
word match zoloft online literature
J Pharmacol Exp Ther. 1983 Sep;226(3):686-700.
Sertraline, 1S,4S-N-methyl-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthylamine, a new uptake inhibitor with selectivity for serotonin.
Koe BK, Weissman A, Welch WM, Browne RG.
Sertraline [1S,4S-N-methyl-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthylamine] was found to be a highly selective and potent competitive inhibitor of synaptosomal serotonin uptake. Sertraline also selectively reduced ex vivo uptake of serotonin and strongly antagonized the serotonin-depleting action of p-chloroamphetamine, indicating potent blockade of serotonin uptake in vivo. Acute and repeated dosing of sertraline decreased serotonin content of whole blood. Sertraline only weakly inhibited rat heart uptake of i.v. [3H]norepinephrine. In substantiation of selective blockade of serotonin uptake, sertraline potentiated various symptoms of 5-hydroxytryptophan but did not reverse reserpine-induced hypothermia. Sertraline was a very weak inhibitor of [3H]quinuclidinyl benzilate binding to rat brain membranes in vitro and did not produce anticholinergic effects in mice in vivo. Sertraline was well tolerated in mice, rats and dogs, with no locomotor stimulant effects in rats or untoward cardiovascular effects in dogs. The major metabolite, N-demethylsertraline, was also a selective serotonin uptake blocker. Sertraline strongly reduced immobility of mice in the Porsolt swim test for antidepressants. After repeated dosing in rats, sertraline diminished the cyclic AMP response of limbic forebrain adenylate cyclase to norepinephrine, as well as the binding of [3H]dihydroalprenolol to cortical membranes. It is proposed that selective blockade of serotonin reuptake can induce activation of norepinephrine neurons and subsequent down-regulation of norepinephrine receptors and that sertraline, a highly selective inhibitor of serotonin uptake, may be an efficacious antidepressant without anticholinergic or cardiovascular side-effects.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6310078&dopt=Abstract
word match zoloft online literature
J Pharmacol Exp Ther. 1995 Nov;275(2):592-7.
N-demethylation of amitriptyline in vitro: role of cytochrome P-450 3A (CYP3A) isoforms and effect of metabolic inhibitors.
Schmider J, Greenblatt DJ, von Moltke LL, Harmatz JS, Shader RI.
Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston Massachusetts, USA.
Biotransformation of amitriptyline (AMI) to its demethylated product nortriptyline (NT) was studied in vitro with human liver microsomes from four different donors, preselected to reflect a range of metabolic rates. Reaction velocity versus substrate concentration was consistent with a sigmoid Vmax model. Vmax varied from 0.42 to 3.42 nmol/mg/min, Km from 33 to 89 microM AMI. Ketoconazole was a highly potent inhibitor of N-demethylation, with a mean Ki value of 0.11 +/- 0.013 microM (+/- S.D.), whereas quinidine (up to 50 microM), a CYP2D6 inhibitor, and alpha-naphthoflavone (up to 5 microM), a CYP1A2 inhibitor only at low concentrations, showed no effect. All selective serotonin reuptake inhibitors (SSRIs) tested had an inhibitory effect on the formation of NT, with mean Ki values of 4.37 (+/- 3.38) microM for sertraline, 5.46 (+/- 1.95) microM for desmethylsertraline, 9.22 (+/- 3.69) microM for fluvoxamine, 12.26 (+/- 5.67) microM for norfluoxetine, 15.76 (+/- 5.05) microM for paroxetine, and 43.55 (+/- 18.28) microM for fluoxetine. A polyclonal rabbit antibody against rat liver CYP3A1, in antibody/microsomal protein ratios varying from 1:1 to 10:1, inhibited N-demethylation of AMI to an asymptotic maximum of 60%. These results are consistent with several case reports describing impairment of AMI metabolism by SSRIs. Inhibition of AMI demethylation by low concentrations of ketoconazole and by anti-3A antibody supports an important role for CYP3A isoforms in mediating this reaction.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7473143&dopt=Abstract
word match zoloft online literature
Herbs and Pharmaceuticals Online ||
Hair Million herbal formula for hair loss and hair growth ||
Antibiotics and prescription medications online literature ||