Disease relevance of F 2207

• Lack of efficacy of the antidepressant milnacipran against visceral stimuli suggests that visceral hypersensitivity may not share the same pharmacology of inhibition as somatic hypersensitivity after nerve injury [1].
• Moreover, in contrast to milnacipran, amitriptyline was responsible for a significant decrease in blood pressure and a significant weight gain [2].
• Efficacy of milnacipran in patients with fibromyalgia [3].
• Milnacipran in the treatment of bulimia nervosa: a report of 16 cases [4].
• Furthermore, studies in patients with liver dysfunction, and in the elderly, suggest that dose adjustment is not necessary when milnacipran is administered to these patients [5].

Psychiatry related information on F 2207

• CONCLUSIONS: The results showed that milnacipran at single doses of up to 100 mg in healthy young volunteers is free from disruptive effects on cognitive function and psychomotor performance [6].
• 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 [7].
• A series of pilot studies have demonstrated the role of milnacipran in the management of certain affective disorders not adequately treated by classical antidepressants [8].
• Possible mechanisms responsible for the difference of action on REM sleep of milnacipran are discussed [9].
• Milnacipran for the drastic improvement of refractory pain in a patient without depressive symptoms: a case report [10].

High impact information on F 2207

• In contrast, no influence of 5-HTT polymorphisms on the antidepressant response to milnacipran was detected [11].
• Prediction of antidepressant response to milnacipran by norepinephrine transporter gene polymorphisms [11].
• METHOD: Ninety-six Japanese patients with major depressive disorder were treated with milnacipran, 50-100 mg/day, for 6 weeks [11].
• The pharmacokinetics of milnacipran and its oxidative metabolites were assessed after the first dose (day 1) and after multiple administration (day 8), and were compared for differences between CYP2D6 and CYP2C19 PMs and EMs [12].
• Lack of interaction of milnacipran with the cytochrome p450 isoenzymes frequently involved in the metabolism of antidepressants [12].

Chemical compound and disease context of F 2207

• The effect of milnacipran (serotonin noradrenaline reuptake inhibitor) on memory in Korsakoff's syndrome after encephalitis [13].
• Milnacipran, venlafaxine and paroxetine did not modify the pain threshold, whereas they have previously been shown to induce anxiolytic-like effects in the FPT [14].
• In C6 glioma cells, midalcipran did not decrease sphingomyelinase activity, at variance with the enzymatic inhibition induced by desipramine (DMI) [15].
• 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 [16].
• Duloxetine and milnacipran appear better tolerated and essentially devoid of cardiovascular toxicity [17].

Biological context of F 2207

• Although further published data are required to confirm its efficacy, good tolerability profile and pharmacokinetic profile which suggests a low potential for drug interactions, milnacipran should be considered a promising agent for the treatment of patients with major depressive disorder [18].
• Of these, milnacipran (1), its N-methyl and N,N-dimethyl derivatives, 7 and 8, respectively, and its homologue 12 at the aminomethyl moiety had binding affinity for the receptor in vitro (IC50: 1, 6.3 +/- 0.3 microM; 7, 13 +/- 2.1 microM; 8, 88 +/- 1.4 microM; 12, 10 +/- 1.2 microM) [19].
• Some are influenced by chirality (e.g. the dealkylation of citalopram and fluoxetine), although information on this aspect of disposition is still lacking for other drugs existing as racemates (e.g. mirtazapine and tianeptine) and milnacipran, which is probably a mixture of 4 stereoisomers [20].
• OBJECTIVES: To elucidate the functional interaction between the stress-induced alteration of synaptic plasticity and therapeutic effects, we examined the anxiolytic mechanism(s) of milnacipran, focusing on modulation of long-term potentiation (LTP) in the hippocampal CA1 field [21].
• The interaction between midalcipran and neurotransmitter receptors and binding sites in the CNS was studied in the rat in comparison with imipramine and desipramine [22].

Anatomical context of F 2207

• Effect of acute, short- and long-term milnacipran administration on rat locus coeruleus noradrenergic and dorsal raphe serotonergic neurons [23].
• Lack of effect of repeated administration of milnacipran, a double noradrenaline and serotonin reuptake inhibitor, on the beta-adrenoceptor-linked adenylate cyclase system in the rat cerebral cortex [24].
• OBJECTIVES: The present study was aimed at characterizing neurochemically and behaviorally the serotonin and noradrenaline reuptake inhibitor (SNRI), milnacipran, in the prefrontal cortex in comparison with tricyclic antidepressants and selective serotonin reuptake inhibitors [25].
• Duloxetine (5-30 mg/kg oral) was also more potent and efficacious than venlafaxine and milnacipran in reversing mechanical allodynia behavior in the L5/L6 spinal nerve ligation model of neuropathic pain [26].
• Peripheral nerve injury sensitizes the response to visceral distension but not its inhibition by the antidepressant milnacipran [1].

Associations of F 2207 with other chemical compounds

• The 5-HT1A antagonist WAY-100635 caused a small potentiation of the effects of milnacipran [27].
• Conformationally restricted analogues of (+/-)-(Z)-2-aminomethyl-1-phenyl-N,N-diethylcyclopropanecarboxamide++ + [milnacipran, (+/-)-1] were designed on the basis of its characteristic cyclopropane structure and were synthesized enantioselectively to develop efficient NMDA receptor antagonists [28].
• The efficacy and the tolerance of milnacipran (100 mg/day), a second generation antidepressant which equipotently inhibits both noradrenaline and serotonin reuptake, was compared to fluoxetine (20 mg/day), a selective serotonin reuptake inhibitor, in two parallel groups of, respectively, 97 and 93 major depressive outpatients [29].
• Interest of a loading dose of milnacipran in endogenous depressive inpatients. Comparison with the standard regimen and with fluvoxamine [30].
• WAY100635 recovered the milnacipran-induced decrease of 5-HIAA levels in the dorsal raphe nucleus to control levels [31].

Gene context of F 2207

• Of these analogs, (1S,2R)-1-phenyl-2-[(S)-1-aminopropyl]-N,N-diethylcyclopropanecarboxamide (PPDC) is 30-fold stronger than milnacipran as an NMDA-receptor antagonist with virtually no inhibitory effect on the neurotransmitter re-uptake [32].
• Patients with lower baseline ACTH levels on day 0 displayed a better clinical outcome when taking the combination of milnacipran and pindolol as shown in the differences in MADRS on day 42 [33].
• Effect of pindolol and milnacipran versus milnacipran and placebo on plasma prolactin and adrenocorticotrophic hormone in depressed subjects [33].
• A series of conformationally restricted analogues of milnacipran, a weak NMDA receptor antagonist, were designed by a method based on allylic strain [34].
• Effect of prolonged exposure to milnacipran on norepinephrine transporter in cultured bovine adrenal medullary cells [35].

Analytical, diagnostic and therapeutic context of F 2207

• A multicenter study compared the antidepressant efficacy and the tolerance of two doses of milnacipran (50 mg and 100 mg/day) and amitriptyline (150 mg/day) in three parallel groups of 45 major depressive inpatients defined by Research Diagnostic Criteria [2].
• The (Z)-enantiomer of midalcipran, at 0.1 microM, displaced to the right the concentration-effect curve of inhibition of release of [3H]5-HT elicited by electrical stimulation induced by LSD [36].
• Milnacipran (30 and 60 mg/kg, PO) significantly reduced the duration of both the immobility time in the forced swimming test and the freezing time in the conditioned fear stress test in rats, which are animal behavioral models for depression and anxiety, respectively [25].
• A subgroup analysis of hospitalized patients in the meta-analysis showed an advantage for milnacipran, suggesting that milnacipran is effective in more severe depression [37].
• There are indications, both from the randomized clinical trials and from the phase IV programme, that milnacipran may have a comparatively rapid onset of action, showing clear signs of efficacy after one week of treatment [8].

References