Drugs online research references
Psychopharmacology (Berl). 1987;92(2):169-72.
Serotonin uptake inhibition during treatment of depression with nortriptyline caused by parent drug and not by 10-hydroxymetabolites.
Malmgren R, Aberg-Wistedt A, Bertilsson L.
Treatment of endogenous depression with nortriptyline (NT), at a daily dose of 150 mg, resulted in a pronounced improvement of seven of ten patients investigated. The concentration of the norepinephrine metabolite HMPG in cerebrospinal fluid (CSF) decreased by 29% (P less than 0.01) after 3 weeks of treatment. There was no significant effect of treatment on the serotonin and dopamine metabolites 5-HIAA and HVA. In previous larger materials, however, a decrease of 5-HIAA in CSF has been demonstrated. Platelets from the patients showed an increase in Km for serotonin uptake in response to NT treatment. The IC50 value of NT for serotonin uptake inhibition was 940 nM, while the corresponding value of the major metabolite of NT, i.e. E-10-OH-NT, was much higher (6700 nM). Thus, during treatment, the parent drug and not the metabolite was responsible for the serotonin uptake inhibition in platelets. There was a close correlation between Km and the plasma concentration of NT after 1 week of treatment (r = 0.88, P less than 0.01) but not after 3 weeks of treatment (r = 0.48; ns). There was no uniform effect of NT treatment on Vmax. It is concluded that clinical NT treatment results in uptake inhibition not only in norepinephrine but also in serotonin neurons.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2440073&dopt=Abstract
Pain. 1987 May;29(2):247-55.
Effect of citalopram, amineptine, imipramine and nortriptyline on stress-induced (footshock) analgesia in rats.
Testa R, Angelico P, Abbiati GA.
The influence of the oral administration of different doses of citalopram (5, 15 and 45 mg/kg), imipramine (15, 30, 45 and 60 mg/kg), nortriptyline (15, 45 and 60 mg/kg) and amineptine (45 mg/kg) on stress-induced analgesia has been studied in anaesthetized rats. None of the administered antidepressants seem to have appreciable analgesic activity when analgesia is tested by the tail-immersion method. Citalopram, imipramine and nortriptyline, but not amineptine, increase the analgesia induced by inescapable footshock delivered continuously for 2 min to rats. Citalopram is the most potent drug. Our results support the suggested importance of 5-HT and noradrenaline terminals, but not those of dopamine, in the mediation of the stress-induced analgesia and seem to support the hypothesis that the analgesic activity of antidepressants is partially related to their modulating effects on the endogenously released opioid peptides involved in the endogenous pain inhibitory systems.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3475664&dopt=Abstract
Life Sci. 1995;57(21):PL339-45.
Influence of antidepressant drugs administration on the morphine inhibitory effect in mice vasa deferentia.
Moreno-Brea MR, Gibert-Rahola J, Mico JA.
Departamento de Neurociencias, Facultad de Medicina, Cadiz, Spain.
The effect of chronic and acute antidepressant drug administration on peripheral opioid mechanisms was investigated. For this purpose, the inhibitory effect of morphine on electrically-induced contractions of mouse vas deferens was measured. Acute antidepressant administration did not induce any change in morphine inhibition. Chronic fluvoxamine and chlorimipramine treatment induced strong and significant hypersensitivity to morphine-inhibition. Chronic desipramine, desmethylclomipramine and nortriptyline treatment induced the opposite effect. These results seem to show differential opioidergic regulation depending on the monoaminergic antidepressant used. The level of this interaction remains to be elucidated.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7475937&dopt=Abstract
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