Drugs online research references
Proc Natl Acad Sci U S A. 1990 Oct;87(19):7522-6.
Chronic antidepressant administration decreases the expression of tyrosine hydroxylase in the rat locus coeruleus.
Nestler EJ, McMahon A, Sabban EL, Tallman JF, Duman RS.
Department of Psychiatry, Yale University School of Medicine, New Haven, CT.
Regulation of tyrosine hydroxylase expression by antidepressant treatments was investigated in the locus coeruleus (LC), the major noradrenergic nucleus in brain. Rats were treated chronically with various antidepressants, and tyrosine hydroxylase levels were measured in the LC by immunoblot analysis. Representatives of all major classes of antidepressant medication-including imipramine, nortriptyline, tranylcypromine, fluvoxamine, fluoxetine, bupropion, iprindole, and electroconvulsive seizures-were found to decrease levels of tyrosine hydroxylase immunoreactivity by 40-70% in the LC. Decreased levels of enzyme immunoreactivity were shown to be associated with equivalent decreases in enzyme mRNA levels. Antidepressant regulation of LC tyrosine hydroxylase appeared specific to these compounds, inasmuch as chronic treatment of rats with representatives of other classes of psychotropic drugs, including haloperidol, diazepam, clonidine, cocaine, and morphine, failed to decrease levels of this protein. The results demonstrate that chronic antidepressants dramatically downregulate the expression of tyrosine hydroxylase in the LC and raise the possibility that such regulation of the enzyme represents an adaptive response of LC neurons to antidepressants that mediates some of their therapeutic actions in depression and/or other psychiatric disturbances.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1977162&dopt=Abstract
Arzneimittelforschung. 1982;32(9):1111-3.
Further assessment of benzodiazepine-tricyclic antidepressant interaction. Effectiveness of combined treatment with ketazolam-nortriptyline on conflict behaviour in rats.
Cannizzaro G, Brucato AF, Provenzano PM.
Using Geller and Seifter's conflict behaviour test, ketazolam in rat increases the rate of responses emitted both with and without punishment. Nortriptyline decrease the non-punished component of the schedule without influencing the punished one. With combined treatment, nortriptyline does not modify the effects of ketazolam on punished responses while nortriptyline, 1 h after administration, decreases, though not significantly, the facilitating action of ketazolam. After 24 h it significantly increases the depressant action of this benzodiazepine. The results suggest that with the combination tricyclic anti-depressant-benzodiazepine, as with these two categories of drugs, there is not always an increase in disinhibiting action, while depressant action has characteristics closely dependent on the properties of the benzodiazepine used.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6128985&dopt=Abstract
Pharmacol Biochem Behav. 1987 Jan;26(1):153-8.
A role for serotonin and beta-endorphin in the analgesia induced by some tricyclic antidepressant drugs.
Sacerdote P, Brini A, Mantegazza P, Panerai AE.
The analgesic effect of acute or chronic nortriptyline, amitriptyline and their effects on morphine induced analgesia were evaluated in the rat. Clomipramine and amitriptyline, but not Nortriptyline, induce analgesia, while all potentiate the effect of morphine when administered acutely. The analgesic effect of clomipramine is blunted by both the serotonin antagonist metergoline and the opiate receptor blocker naloxone, thus indicating an involvement of both the serotoninergic and endogenous opioid system. The involvement of the serotoninergic system is confirmed by the similar results obtained with the serotonin precursor 5-hydroxytryptophan administered alone or together with morphine. A relation between the serotoninergic and the endogenous opioid systems is also shown by the increase in hypothalamic beta-endorphin concentrations elicited by all the drugs used after acute or chronic treatment, with the only exception of nortriptyline, that has been shown to exert its effects mainly through the noradrenergic system. In conclusion, the analgesic effect of clomipramine and amitriptyline and their potentiation of morphine induced analgesia seems to be related to an activation of the endogenous opioid system mediated by serotonin.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2951743&dopt=Abstract
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