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Functional abdominal disorders
Published in Michael JG Farthing, Anne B Ballinger, Drug Therapy for Gastrointestinal and Liver Diseases, 2019
Bernard Coulie, Michael Camilleri
Table 8.1 summarizes placebo-controlled trials of antidepressants in IBS. In two large studies,143,144 trimipramine decreased abdominal pain, nausea and depression but did not alter stool frequency. The beneficial effect seems to be greater in those with abdominal pain and diarrhea.139,145 Tricyclic antidepressants do not result in improvement in constipation-predominant IBS, probably reflecting an anticholinergic effect. There is increasing interest in the potential application of SSRIs which tend not to cause constipation and may even induce diarrhea in some patients.146 Their role is currently the focus of prospective studies. One uncontrolled study supports the efficacy of SSRIs in treating patients with IBS.60
Substrates of Human CYP2D6
Published in Shufeng Zhou, Cytochrome P450 2D6, 2018
Trimipramine, a tricyclic antidepressant used in the treatment of depression, is a moderate reuptake inhibitor of norepinephrine, and a weak reuptake inhibitor of serotonin and dopamine (Gastpar 1989). 2-Hydroxytrimipramine and 2,10- or 2,11-dihydroxytrimipramine are formed in vitro by CYP2D6 (Figure 3.9) (Bolaji et al. 1993). Acetylation of the latter metabolite results in dehydration at C10 to give 10,11-dehydro-2-acetoxytrimipramine. N-Glucuronide and glucuronides of the hydroxylated metabolites are also detected in human urine. A stereoselectivity in the metabolism of trimipramine has been observed, with a preferential N-demethylation of (D)-trimipramine and a preferential hydroxylation of (L)-trimipramine (Eap et al. 2000). CYP2D6 catalyzes the 2-hydroxylation of (L)-trimipramine and (L)-and (D)-desmethyltrimipramine, but not of (D)-trimipramine. CYP2C19, but not CYP2D6, is involved in the demethylation pathway, with a stereoselectivity toward (D)-trimipramine. CYP3A4/5 appears to be involved in the metabolism of (L)-trimipramine to an unidentified metabolite. The CYP2D6 inhibitor quinidine increases the plasma concentration of trimipramine but the formation of 2-hydroxytrimipramine is decreased (Eap et al. 1992). Cases have been reported on increased trimipramine levels by coadministered paroxetine (Leinonen et al. 2004). A fatal case has been documented where trimipramine and citalopram are coadministered (Musshoff et al. 1999).
Cyclodextrins improving the physicochemical and pharmacological properties of antidepressant drugs: a patent review
Published in Expert Opinion on Therapeutic Patents, 2018
Tâmara Coimbra Diniz, Tiago Coimbra Costa Pinto, Paula dos Passos Menezes, Juliane Cabral Silva, Roxana Braga de Andrade Teles, Rosana Christine Cavalcanti Ximenes, Adriana Gibara Guimarães, Mairim Russo Serafini, Adriano Antunes de Souza Araújo, Lucindo José Quintans Júnior, Jackson Roberto Guedes da Silva Almeida
The aqueous solutions of imipramine or its derivate trimipramine have two disadvantages: on the one hand, they are very bitter, which makes their oral administration not readily acceptable, especially for children and elderly people; on the other hand, the division of aqueous forms is always a problem, in outpatient treatment, especially for elderly people. The invention US5244881 resolves the two abovementioned disadvantages. Trimipramine methanesulphonate was dissolved in water, CD was wetted with the solution and mixed for 2 h at ambient temperature before being lyophilized. Another experiment was performed in which the paste was placed in a crystallizer and then placed in a heated desiccator at 60°C overnight. After drying, either lyophilizates, which are non-sticky to the touch, are obtained in the first case or a perfectly fluid powder is obtained in the second case [62].