Determination of clomipramine by flow‐injection analysis with acidic potassium permanganate–formic acid chemiluminescence detection

A sensitive and simple chemiluminescent (CL) method for the determination of clomipramine has been developed by combining the flow‐injection analysis (FIA) technique, which is based on the CL intensity generated from the redox reaction of potassium permanganate (KMnO₄)–formic acid in sulphuric acid (H₂SO₄) medium. Under the optimum conditions, the linear range for the determination of clomipramine was 0.04–4 µg/mL, with a correlation coefficient of 0.9988 (n = 10) and a detection limit of 0.008 µg/mL (3σ), and the relative standard deviation (RSD) for 2.0 µg/mL clomipramine (n = 11) is 1.26%. The proposed method has been successfully applied to the determination of the studied clomipramine in pharmaceutical preparations. The possible reaction mechanism is discussed. Copyright © 2011 John Wiley & Sons, Ltd.     

Chronic administration of the antidepressants phenelzine,despiramine, clomipramine,or maprotiline decreases binding to 5-hydroxytryptamine2A receptors without affecting benzodiazepine binding sites in rat brain

Summary 1. The effects of chronic administration of five antidepressant drugs on the benzodiazepine and 5-HT_2A binding sites in the same rat brain were assessed.2. Clomipramine, desipramine, maprotiline, fluoxetine, and phenelzine (all 10 mg/kg/day) were administered s.c. for 21 days by Alzet osmotic minipumps.3. Results showed that none of the drugs changed the density or affinity of benzodiazepine binding sites, yet at the same dose all the drugs with the exception of fluoxetine decreased binding to 5-HT_2A receptors in the same animals.     

Safety and mechanism of appetite suppression by a novel hydroxycitric acid extract (HCA-SX)

A growing body of evidence demonstrates the efficacy of Garcinia cambogia-derived natural (–)-hydroxycitric acid (HCA) in weight management by curbing appetite and inhibiting body fat biosynthesis. However, the exact mechanism of action of this novel phytopharmaceutical has yet to be fully understood. In a previous study, we showed that in the rat brain cortex a novel HCA extract (HCA-SX, Super CitriMax) increases the release/availability of radiolabeled 5-hydroxytryptamine or serotonin ([³H]-5-HT), a neurotransmitter implicated in the regulation of eating behavior and appetite control. The aim of the present study was 2-fold: (a) to determine the effect of HCA-SX on 5-HT uptake in rat brain cortex in vitro; and (b) to evaluate the safety of HCA-SX in vivo. Isolated rat brain cortex slices were incubated in oxygenated Krebs solution for 20 min and transferred to buffer solutions containing [³H]-5-HT for different time intervals. In some experiments, tissues were exposed to HCA-SX (10 M – 1 mM) and the serotonin receptor reuptake inhibitors (SRRI) fluoxetine (100 M) plus clomipramine (10 M). Uptake of [³H]-5-HT was expressed as d.p.m./mg wet weight. A time-dependent uptake of [³H]-5-HT occurred in cortical slices reaching a maximum at 60 min. HCA-SX, and fluoxetine plus clomipramine inhibited the time-dependent uptake of [³H]-5-HT. At 90 min, HCA-SX (300 M) caused a 20% decrease, whereas fluoxetine plus clomipramine inhibited [³H]-5-HT uptake by 30%. In safety studies, acute oral toxicity, acute dermal toxicity, primary dermal irritation and primary eye irritation, were conducted in animals using various doses of HCA-SX. Results indicate that the LD₅₀ of HCA-SX is greater than 5000 mg/kg when administered once orally via gastric intubation to fasted male and female Albino rats. No gross toxicological findings were observed under the experimental conditions. Taken together, these in vivo toxicological studies demonstrate that HCA-SX is a safe, natural supplement under the conditions it was tested. Furthermore, HCA-SX can inhibit [³H]-5-HT uptake (and also increase 5-HT availability) in isolated rat brain cortical slices in a manner similar to that of SRRIs, and thus may prove beneficial in controlling appetite, as well as treatment of depression, insomnia, migraine headaches and other serotonin-deficient conditions.     

Hypersensitivity of the Corticotropic Axis to the Serotoninergic Agent Clomipramine in Obese Women

Serotoninergic control of food intake has been shown to be abnormal in obese persons with a decrease in serotoninergic tone. The neuroendocrine effects of intravenous I.V. administration of clomipramine (CMI), a serotonin uptake inhibitor, were studied in normal-weight (n=7) and obese subjects before (n=12) and after (n=6) dietary restriction. Under double-blind, placebo-controlled conditions, a single 12.5 mg dose of CMI was administered. There was no difference in baseline values of prolactin (PRL), corticotropin (ACTH) and cortisol in non-obese controls, obese before and obese after weight loss. CMI led to significant increases of PRL, ACTH, and cortisol concentrations in the controls as well as the obese group. The ACTH and cortisol responses to CMI in obese subjects were somewhat greater than the responses in normal-weight subjects. The area under the curve AUC for ACTH after clomipramine was 6202 ± 976 pg/ml.150 minutes for the obese before weight loss and 3274 ± 512 pg/ml.150 minutes for the controls and the difference was significant at the level of p=0.052. The cortisol peak value after clomipramine was 163.71 ± 14.31 ng/ml in the non-obese and 214.66 ± 12.59 ng/ml in the obese (p=0.025). However, there was no difference in the obese subjects before and after weight loss. These data support the assumption that obese women have an abnormal sensitivity to the serotoninergic control of the hypothalamic pituitary adrenal axis (HPA), and that a mild weight loss does not significantly modify their serotoninergic tone.     

The Effect of Antidepressant Drugs on 24-Hour Rhythms of Tryptophan Metabolism in the Rat

The effect of three antidepressant drugs, imipramine hydrochloride, clomipramine hydrochloride and zimelidine dihydrochloride on plasma free and total TRY concentrations has been examined.

The drugs were administered to male Wistar rats in the drinking water at a concentration of 200μgml^-1 for up to 15 days. The effects of TRY concentration were complex and, after 2 days, inconsistent. After 14 days, the overall effect of imipramine was to lower free TRY levels and abolish 24-hr variation in free TRY concentration. Zimelidine and clomipramine tended to increase free TRY, particularly at 1300h so that the overall effect was to delay the peak in plasma-free TRY until later in the day. The possible significance of these findings to the mechanism of action of antidepressant drugs in clinical practice is discussed.