Posted by iris2 on September 7, 2004, at 16:03:23
In reply to Re: what is Milnacipran?, posted by Racer on September 7, 2004, at 12:41:32
I think so. You could google Ixel if you are not finding Milnacipran.
Here's some stuff off of one site:
It is possible that duloxetine (Cymbalta), due to be FDA-licensed in 2004, and milnacipran (Ixel), available in Europe, may be more effective than venlafaxine for a segment of the population that can benefit from dual serotonin-noradrenaline reuptake inhibition. Pain-ridden and melancholic depressives in particular may respond well to this class of drug. Once again, dopaminergic augmentation may be beneficial for the naturally lethargic. Unlike venlafaxine, duloxetine exerts its more balanced serotonin and noradrenaline reuptake inhibition throughout the dosage range. Duloxetine also weakly inhibits the reuptake of dopamine, and shows minimal affinity for the histamine and cholinergic muscarinic receptors. But it takes time to separate genuine therapeutic advance from drug company hype, typically not until the patent expires.
Milnacipran (Ixel) is a new antidepressant with essentially equal potency for inhibiting the reuptake of both serotonin and noradrenaline, with no affinity for any neurotransmitter receptor studied. A review of the studies comparing milnacipran, placebo and active comparator antidepressants provides clear-cut evidence of its efficacy in both severe and moderate depression in hospitalized and community settings. Meta-analyses of the original data of controlled trials involving 1032 patients, comparing milnacipran with imipramine or selective serotonin reuptake inhibitors (SSRIs), show that milnacipran provides antidepressant efficacy similar to that of imipramine and significantly superior to that of the SSRIs. An analysis of a database of over 3300 patients shows that both the general and cardiovascular tolerability of milnacipran are superior to those of the tricyclic antidepressants (TCAs) with fewer cholinergic side-effects. The tolerability of milnacipran was comparable to that of the SSRIs, with a higher incidence of dysuria with milnacipran, and a higher frequency of nausea and anxiety with the SSRIs. Milnacipran is a new therapeutic option in depression, which offers a clinical efficacy in the range of the TCAs combined with a tolerability equivalent to that of the SSRIs.
Milnacipran (Ixel) is a new antidepressant which has been developed for its selective inhibition of both serotonin and noradrenaline reuptake and its lack of affinity for neurotransmitter receptors. It inhibits virtually equipotently the reuptake of serotonin and noradrenaline both in vitro and in vivo, as demonstrated by the antagonism of centrally acting monoamine displacers. It has no effect on dopamine reuptake. In addition, milnacipran has been shown by intracerebral microdialysis to increase the extracellular levels of both serotonin and noradrenaline after acute administration. Milnacipran is devoid of interactions at any known neurotransmitter receptor or ion channel. In particular, and unlike tricyclic antidepressants, it does not act at noradrenergic, muscarinic or histaminergic receptors. Contrary to tricyclic antidepressants, chronic administration of milnacipran does not modify beta-adrenoceptor binding or second messenger function. Milnacipran is active on various animal models of depression such as the forced swimming test in the mouse, learned helplessness in the rat and the olfactory bulbectomized rat model. This pharmacological profile, associated with an excellent bioavailability in man, was predicted to be that required for a powerful and well-tolerated antidepressant. Subsequent clinical development has shown this prediction to be well founded.
Milnacipran (MIL) is a representative of a new class of antidepressants (SNRIs) which inhibit the reuptake of serotonin and noradrenaline, but, in contrast to tricyclics, show no affinity for neurotransmitters receptors. The present study was aimed at determining whether repeated MIL administration (given at doses of 10 or 30 mg/kg, twice daily for 14 days) induced the adaptive changes in the dopaminergic system similar to those reported by us earlier for tricyclic antidepressants. The obtained results showed that MIL administered repeatedly did not change the responsiveness of dopamine D1 receptors since it did not change the SKF 38393-induced grooming. Repeated MIL treatment increased the hyperlocomotion induced by D-amphetamine and 7-OH-DPAT, but did not affect the D-amphetamine and apomorphine stereotypies. The binding parameters (Bmax and Kd) to dopamine D1 and D2 receptors in the limbic forebrain were not affected by repeated MIL treatment when [3H]SCH 23390 and [3H]spiperone, respectively, were used as ligands. On the other hand, the increased density of dopamine D2 receptors (Bmax) was observed in the striatum after repeated treatment with MIL. MIL administered acutely or repeatedly did not change the binding of [3H]7-OH-DPAT to dopamine D3 receptors in the islands of Calleja and the shell region of the nucleus accumbens septi. The above results indicate that repeated MIL administration induces the adaptive changes in the dopaminergic system, especially it enhances the functional responsiveness of dopamine D2 and D3 receptors. However, the question whether this increased functional responsiveness is important for the clinical antidepressant efficacy, remains open.
OBJECTIVE: The principal objective was to compare the effects of milnacipran, an antidepressant characterized by a dual-action on serotonin and noradrenaline reuptake, with placebo on memory, attention and psychomotor performance in healthy volunteers. The secondary objective was to evaluate the effects of milnacipran on mood, anxiety and vigilance in these subjects. METHODS: In a double-blind crossover randomized trial, milnacipran (50 mg b.d.) or placebo was administered during two periods of 7 days separated by a washout period of 7 days. Memory tests (recall of words, images and coloured bars), tests to evaluate attention and vigilance (squares test, critical flicker fusion test and choice reaction time test) and visual analogue scales for affect and sleep were used. RESULTS: There were no significant differences between milnacipran and placebo groups with respect to the psychomotor functions tested. No differences were observed in the Norris scales for vigilance, anxiety or satisfaction or in the sleep questionnaire (sleep latency, sleep quality and waking). CONCLUSION: Milnacipran, administered at 100 mg per day for 7 days to healthy volunteers, had no effects on cognitive functions.
irene
poster:iris2
thread:380308
URL: http://www.dr-bob.org/babble/20040904/msgs/387715.html