A randomized double-blind placebo-controlled study of tropisetron in the treatment of outpatients with generalized anxiety disorder

Abstract

The selective 5HT3 antagonist tropisetron was studied in 91 outpatients meeting DSM-III criteria for Generalized Anxiety Disorder. Following a placebo washout period of up to 1 week, one of three active treatments (tropisetron 0.5 mg, 5 mg, or 25 mg daily) or placebo was given for a further 3 weeks. After 7 days treatment termination rates due to inefficacy showed a statistically significant dose-related therapeutic effect of tropisetron. Similar effects were seen on the Hopkins Symptom Check List total score and the Global Impression Scale. The Hamilton Anxiety Scale showed a similar trend which, however, failed to reach statistical significance. At day 21 tropisetron showed significant dose-dependent effects on all anxiety-related outcome measures. The incidence of adverse events was low and the severity generally mild. Most frequent complaints were headache, nausea, constipation and nervousness. Laboratory tests and physical examination performed at baseline and study end showed no significant treatment effects.

Neuropharmacological evaluation of a novel 5-HT3 receptor antagonist (4-benzylpiperazin-1-yl)(3-methoxyquinoxalin-2-yl) methanone (6g) on lipopolysaccharide-induced anxiety models in mice

“…Serotonergic signaling in prefrontal cortex demonstrates an important role in regulating sensation, emotion, and memory under normal and pathological conditions. Increased availability of 5-HT over 5-HT 2 and 5-HT 3 receptors increases anxiety, while blockade of 5-HT 3 receptors produces anxiolytic-like effect [10,11]. Several preclinical and clinical studies have suggested that 5-HT 3 receptors may be a relevant target in the treatment of affective disorders such as anxiety and depression [11][12][13][14].…”

Synthesis and SAR of N-Chlorophenyl Substituted Piperrazinylethyl-aminomethylpyrazoles as 5-HT3AInhibitors

“…According to the structure activity relationships (SAR) studies of aromatic substituents (Ar) on piperazine, p-chlorophenyl group (a series of 7) tends to exhibit better activities than those of other functional groups such as phenyl group (6), m-chlorophenyl group (8), and p-chlorophenyl(phenyl)methyl substituted ones (9). Among the p-chlorophenypiperazine substituted compounds, the compound 7b and 7h having one n-propyl group in pyrazole ring, were the most potent inhibitor that exhibited IC 50 values of 1.3 µM, which were comparable to the well-known 5-HT3A receptor antagonist MDL-72222 (Table 1).…”

“…6 In CNS, 5-HT 3A receptors are known for nausea and vomiting, whereas are known for visceral pain such as irritable bowel syndrome in PNS. 7,8,9,10,11 In the early 1990s the introduction of 5-HT3 receptor antagonists into markets was perceived great success to attenuate side effects related with chemotherapy-induced emesis. It is well known that nausea and vomiting induced by chemotherapy of cancer patients result from activation of 5-HT3A receptors in the brain stem.…”

“…12 In present study, we designed novel skeletons based on known 5-HT3 antagonists for the development of novel 5-HT3A antagonists. Thus, we developed novel target molecule (6)(7)(8)(9), called N-chlorophenyl substituted piperazinylethylaminomethylpyrazole, which is contained piperazine ring, chlorophenyl and pyrazole group (Fig. 2).…”

Effects of 5HT3 Receptor Antagonism by Tropisetron on the Sleep EEG and on Nocturnal Hormone Secretion

“…In rats, the compound was shown to be capable to reduce aversive properties of drug stimuli (Acquas et al 1990). In a re cent clinical trial, an anxiolytic effect of tropisetron was found in patients with generalized anxiety disorder (Lecrubier et al 1993). The present study explores the effects of the 5HT 3 antagonist tropisetron on sleep and sleep-associated secretion of cortisol and growth hor mone (GH) in humans.…”