Imipramine side effects profile

Antidepressants are used in the treatment of neuropathic pain and headache. They include the classic tricyclic compounds and are divided into nonselective nor-adrenaline/5-HT reuptake inhibitors (e.g., amitriptyline, imipramine, clomipramine, venlafaxine), preferential noradrenaline reuptake inhibitors (e.g., desipramine, nortriptyline) and selective 5-HT reuptake inhibitors (e.g., citalopram, paroxetine, fluoxetine). The reuptake block leads to a stimulation of endogenous monoaminer-gic pain inhibition in the spinal cord and brain. In addition, tricyclics have NMDA receptor antagonist, endogenous opioid enhancing, Na+ channel blocking, and K+ channel opening effects which can suppress peripheral and central sensitization. Block of cardiac ion channels by tricyclics can lead to life-threatening arrhythmias. The selective 5-HT transporter inhibitors have a different side effect profile and are safer in cases of overdose [3]. 

Pharmaceutical Comparison. At least 8 studies to date have examined the effectiveness of hypericum compared to the pharmaceutical antidepressants imipramine, amitriptyline, and maprotiline. Preliminary results indicate that hypericum is equivalent to standard antidepressants in effectiveness (Linde et al. 1996 Vorbach 1997). Similar to the pharmaceutical antidepressants, there is a 10-14 day lag for therapeutic effects of hypericum (Harrer et al. 1994). Indeed, the differences seen between hypericum and placebo groups becomes apparent between 2 and 4 weeks (Sommer and Harrer 1994). Hypericum has been reported to have a more favorable side-effect profile than several pharmaceutical antidepressants as well (Vorbach et al. 1994 Harrer et al. 1994). In double-blind studies, subjects have reported fewer and less-severe side effects. Although these initial results are promising, Linde and colleagues (1996) have concluded that the present evidence is inadequate to establish... 

The TCAs appear to reduce symptoms of reexperiencing and depression related to PTSD. In children and adolescents, imipramine may be an effective agent for ASD symptoms, especially traumatic experiences or flashbacks related to sleep onset and sleep maintenance (Robert et al., 1999). Because of their safety and side effect profile and the apparent lack of effectiveness in childhood depression, the TCAs have been supplanted by the SSRIs as first-line pharmacotherapy in the treatment of depression and anxiety in childhood. As such, these agents should be reserved for second- or third-line treatment in pediatric PTSD. 

The SSRIs, due to their superior tolerability and side-effect profile, are currently considered the first-line treatment for the long-term treatment of dysthymic disorder. In the case of failure or intolerance to SSRIs, the TCAs amitriptyline, desipramine, and imipramine or the reversible MAOl moclobemide should be tried. The reversible MAOl phenelzine has shown superior effectiveness to imipramine in one double-blind study. However, it should be reserved as third-line therapy due to its less-favorable side-effect profile and dietary restrictions. 

Currently accepted (US FDA-approved) first-line treatments for GAD are the serotonin and nonepinephrine reuptake inhibitor (SNRi) veniafaxine (75-225 mg/day). - or the seiective serotonin reuptake inhibitor (SSRi) paroxetine (20-50 mg/day). However, it seems that the other SNRis/SSRis may prove to be as efficient. Among the tricyciic antidepressants (TCAs), imipramine (75-200 mg/day) has been the most widely studied and has shown beneficial results. However, due to its relatively unfavorable side-effect profile compared with veniafaxine and the SSRIs, this drug might be the second choice in treating GAD. 

BW 247 and protriptyline were Inactive.75 bw 247 (15) is a ring-opened TCA with few anticholinergic effects and a profile of mixed NA and 5-HT uptake inhibition. It is structurally related to several potential antidepressants, including AHR 1118 (16). Both 1 and 1 are effective antidepressants in man 6 showed fewer side-effects than imipramine in a... 

Milnacipran selectively inhibits the reuptake of 5-HT (selectivity ratio, 9) at the presynaptic membrane site, thus increasing the concentration of 5-HT in the synaptic cleft (69). Although milnacipran is not a TCA, its mechanism of action is similar to that of imipramine, and its binding and reuptake inhibition profile more closely resembles that of the TCAs. Milnacipran has weak affinity for adrenergic, muscarinic, and Hi receptors and, therefore, is expected to be devoid of the prominent side effects observed for the TCAs. In clinical studies, milnacipran showed antidepressant efficacy similar to that of TCAs and SSRIs. 

Since their introduction in the 1980s, selective serotonin reuptake inhibitors (SSRls) such as paroxetine, fluoxetine, and citalopram have enjoyed tremendous clinical and commercial success due to their improved safety profile when compared with first-generation tricyclic antidepressants like imipramine. Nevertheless, they still display several side effects including gastrointestinal distress, anxiety, insomnia, weight gain, and sexual dysfunction. Like other current antidepressants. 

PAMPA-pKa fiux optimized design (pOD)-permeabiiity Iso-pH mapping unstirred PAMPA was used to measure the effective permeability, Pe, as a function of pH from 3 to 10, of five weak monoprotic acids (ibuprofen, naproxen, ketoprofen, salicylic acid, benzoic acid), an ampholyte (piroxicam), five monoprotic weak bases (imipramine, verapamil, propranolol, phenazopyridine, metoprolol), and a diprotic weak base (quinine). The intrinsic permeability, Po, the UWL permeability, Pu, and the apparent pKa (pKa.fiux) were determined from the pH dependence of log Pg. The underlying permeability-pH equations were derived for multiprotic weak acids, weak bases, and ampholytes. The average thickness of the UWL on each side of the membrane was estimated to be nearly 2000 p, somewhat larger than that found in Caco-2 permeability assays (unstirred). As the UWL thickness in the human intestine is believed to be about forty times smaller, it is critical to correct the in vitro permeability data for the effect of the UWL. Without such correction, the in vitro permeability coefficient of lipophilic molecules would be indicative only of the property of water. In single-pH PAMPA (e.g., pH 7.4), the uncertainty of the UWL contribution can be minimized if a specially selected pH (possibly different from 7.4) were used in the assay. From the analysis of the shapes of the log Pe-pH plots, a method to improve the selection of the assay pH, called pOD-PAMPA, was described and tested. From an optimally selected assay pH, it is possible to estimate Pg, as well as the entire membrane permeability-pH profile. 

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