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netvision.net.il
The antinociceptive effects of the novel phentylethylamine antidepressant drug venlafaxine and its interaction with various opioid, noradrenaline and serotonin receptor subtypes were evaluated. When mice were tested with a hotplate analgesia meter, venlafaxine induced a dose-dependent antinociceptive effect following i.p. administration with an ED50 of 46.7 mg/kg (20.5; 146.5; 95% CL). Opioid, adrenergic and serotoninergic receptor antagonists were tested for their ability to block venlafaxine antinociception. Venlafaxine-induced antinociception was significantly inhibited by naloxone, nor-BNI and naltrindole but not by beta-FNA or naloxonazine, implying involvement of kappa1- and delta-opioid mechanisms. When adrenergic and serotoninergic antagonists were used, yohimbine (P < 0.005) but not phentolamine or metergoline, decreased antinociception elicited by venlafaxine, implying a clear alpha2- and a minor alpha1-adrenergic mechanism of antinociception. When venlafaxine was administered together with various agonists of the opioid and alpha2- receptor subtypes, it significantly potentiated antinociception mediated by kappa1- kappa3- and delta-opioid receptor subtypes. The alpha2-adrenergic agonist clonidine significantly potentiated venlafaxine-mediated antinociception. Summing up these results, we conclude that the antinociceptive effect of venlafaxine is mainly influenced by the kappa- and delta-opioid receptor subtypes combined with the alpha2-adrenergic receptor. These results suggest a potential use of venlafaxine in the management of some pain syndromes. However, further research is needed in order to establish both the exact clinical indications and the effective doses of venlafaxine when prescribed for pain.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10505622&dopt=Abstract
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Life Sci. 1999;65(17):1773-86.
Differential effect of chronic antidepressant treatments on lipopolysaccharide-induced depressive-like behavioural symptoms in the rat.
Shen Y, Connor TJ, Nolan Y, Kelly JP, Leonard BE.
Department of Pharmacology, National University of Ireland, Galway.
In the present study we observed that lipopolysaccharide (LPS) administration provoked a characteristic reduction in body weight gain, food consumption, saccharin (but not water) consumption and nocturnal locomotor activity. It has been previously suggested that the ability of LPS to suppress the consumption of, and preference for, a palatable solution such as saccharin without altering water consumption, may represent an anhedonic response. The results of the present study demonstrate that chronic treatment with the tricyclic antidepressant (TCA) desipramine (7.5 mg/kg; i.p.) prevented LPS-induced anorexia, loss of body weight, the antidipsogenic effect and hypoactivity. In contrast, chronic treatment with the antidepressants paroxetine (7.5 mg/kg; i.p.) and venlafaxine (10 mg/kg; i.p.) failed to alter any of the LPS-induced behavioural responses. Furthermore, chronic treatment with desipramine (and to a lesser extent paroxetine) reduced the consumption of, and preference for, saccharin suggesting that these antidepressant treatments induce an "anhedonic" response in their own right. In conclusion, chronic desipramine treatment attenuated LPS-induced depressive-like behavioural symptoms in the rat. However, chronic treatment with paroxetine and venlafaxine did not significantly alter LPS-induced behavioural responses. The results of the present study support the hypothesis that TCA's may exert part of their anti-depressive efficacy through their effects on the immune system. However, this property does not appear to be shared by newer antidepressants which possess a better side effect profile than the TCA's. The suppressive effect of TCA's on proinflammatory cytokine secretion is discussed as a mechanism by which these agents alter LPS-induced behavioural responses.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10576557&dopt=Abstract
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columbia.edu
There is a longstanding belief that personality represents a structure that is stable over time, and changes, if at all, very slowly. Nonetheless, clinical and empirical evidence suggests that in patients with some Axis I disorders, the rate of personality disorders using DSM criteria decreases after treatment, suggesting that personality as assessed by phenomenological systems is state-dependent. An alternative to the DSM phenomenological system of conceptualizing personality is the dynamic concept of character, that is, a predictable pattern of both adaptive and pathological defense mechanisms, and personality organization comprised of object relations, ego strengths, and superego development. Data from this study address the hypothesis that defense mechanisms and personality organization remain relatively stable in patients treated for Axis I disorders, irrespective of clinical improvement. Patients meeting DSM-IV criteria for major depressive disorder (MDD) entered randomized, controlled medication trials. Defensive functioning was evaluated with the Defense Style Questionnaire (DSQ) [Bond et al., 1983: Arch Gen Psychiatry 40:333-338], and personality organization was assessed with the Inventory of Personality Organization (IPO; Clarkin et al., unpublished), both at baseline and at the completion of the clinical trial. Data were analyzed for whether an individual's pattern of defense mechanisms and personality organization were stable over time regardless of response to treatment of MDD. The question was also asked whether a predominant pattern of defense mechanisms or level of personality organization predicts response to treatment or dropout rate. Among treatment responders, nonresponders and drop-outs, baseline DSQ scores were similar except for "image-distorting" defenses, which were significantly more prevalent among drop-outs compared to responders (P = .016). Post-treatment DSQ values revealed a significant decrease in "maladaptive" defenses (P = .01) in the entire sample, while intermediate and "adaptive" defenses remained unchanged. This same pattern was found to hold true in treatment responders. When comparing treatment responders and nonresponders at the end of the trial, medication responders used significantly less "maladaptive" defenses than did nonresponders (P = .003), and had a significantly higher, or healthier level of "overall defensive functioning" (P = .04). Baseline and post-treatment IPO values did not show significant differences. Results of the study address the question of whether there are personality characteristics that are enduring and that can be appreciated irrespective of an Axis I disorder.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10690578&dopt=Abstract
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