Determination of opipramol in human plasma by high-performance liquid chromatography with photometric detection using a cyanopropyl column.

A high-performance liquid chromatographic method is described for the determination of opipramol in human plasma. Opipramol was extracted into tert.-butylmethyl ether, separated on a cyanopropyl silica column and detected at 254 nm. Imipramine was used as internal standard. The limit of quantitation was 250 pg/ml using 1.5 ml plasma. Precision was better than 9%, inaccuracy less than 8%. The assay is more sensitive than previously published methods, and it has been applied to the analysis of plasma samples from a pharmacokinetic study.

Opipramol for the treatment of generalized anxiety disorder: a placebo-controlled trial including an alprazolam-treated group.

Opipramol, a drug widely prescribed in Germany, is a tricyclic compound with no reuptake-inhibiting properties. However, it has pronounced D2-, 5-HT2-, and H1-blocking potential and high affinity to sigma receptors (sigma-1 and sigma-2). In early controlled trials, anxiolytic effects were revealed. However, those studies were performed before the concept of generalized anxiety disorder (GAD) was established. Because of the interesting receptor-binding profile and promising results of the early clinical trials, the authors performed a state-of-the-art placebo-controlled trial using alprazolam as an active control. Three hundred seven outpatients with GAD were included. After a 7-day single-blind placebo washout, patients were randomly assigned to receive either opipramol (final dose, 200 mg/day), alprazolam (2 mg/day), or placebo and were treated for 28 days. The efficacy of both active compounds was higher than the effects with placebo treatment. There were statistically significant differences (p < 0.05, according to the analysis of covariance) in the main outcome criterion (baseline-adjusted final means of an intent-to-treat analysis of the total scores on the Hamilton Rating Scale for Anxiety) and in secondary efficacy parameters, with global improvement of 47% for placebo and significantly more for opipramol (63%) and alprazolam (64%). Regarding safety and tolerability, no substantial differences in the number of adverse events observed between treatment groups were obvious. Sedation seemed more pronounced with alprazolam treatment than with opipramol or placebo. In this trial, it was demonstrated for the first time that opipramol, a strong but nonselective sigma site ligand, possesses anxiolytic efficacy superior to placebo in the treatment of GAD.

Identification and determination of opipramol metabolites in plasma and urine.

In six cases of suspected opipramol overdose, commercially available immunoassays for tricyclic antidepressants (TCA) EMIT tox serum Assay and ADxR serum TCA Assay indicated arbitrarily high or toxic TCA concentrations. However, opipramol concentrations determined by high-performance liquid chromatography (HPLC) analysis were in the high-normal or low-toxic range. This finding prompted us to study opipramol metabolism by mass spectral techniques and to determine the cross-reactivity of opipramol and its metabolites in immunoassays. Three previously unknown metabolites (I, II, V) included an oxidation product of the hydroxyethyl moiety to an acetic acid group at the piperazine side chain (1), a decarboxylation product of the latter metabolite (II), and opipramol-N-oxide (V). In addition, two previously reported metabolites were identified, which included a deshydroxyethyl metabolite (III) and dibenzazepine (IV). One of the major metabolites of opipramol is the acetic acid metabolite (I), which may exceed the opipramol plasma concentration immensely and contribute to an arbitrarily high concentration in commercially available immunoassays. The cross-reactivities of the metabolite (I) were determined to be 64 and 66% with EMIT and ADx, respectively.

Chromatographic analysis (TLC) of fluoxetine, doxepine, imipramine and opipramol in human plasma.

Fluoxetine, imipramine, doxepine and opipramol after liquid-liquid extraction were separated by TLC on silica gel 60 GF254 by ascending and horizontal technique using suitable mobile phases. The substances were identified by UV irradiation at 254 nm and by spraying of Amelinka's reagnet (up to the amount 0.25 microgram fluoxetine and 0.05 microgram imipramine, doxepine and opipramol).