Initial study of methylclonazepam in generalized anxiety disorder

Abstract

The anxiolytic activity of methylclonazepam was compared to lorazepam and placebo in a double-blind, randomized cross-over study, using a latin square design, in 18 inpatients meeting Research Diagnostic Criteria for Generalized Anxiety Disorders. Patients presented at least 1 year of symptomatology and had a minimum score of 20 on the Hamilton Anxiety Scale, despite chronic anxiolytic pharmacotherapy. Daily dosage was flexible, from three to six tablets of methylclonazepam 1 mg, lorazepam 2.5 mg, or placebo. Clinical evaluation included Hamilton Anxiety Scale, Clinical Global Impression (CGI), a side-effects checklist, completed every 2 days, and the global preference of the patient for one of the treatment periods. Results showed a highly significant superiority of both benzodiazepines over placebo on the Hamilton Scale (P less than 0.000001) and CGI (P less than 0.001), and also a significant superiority of methylclonazepam over lorazepam on the Hamilton Scale (P less than 0.01), CGI-1 (P less than 0.01), and in the number of patient preferences (14 versus 1; P less than 0.001), with no significant differences in side-effects or related to position in the trial. These results support the value of the cross-over design in chronic and severe anxious inpatients for the demonstration of differences in efficacy between anxiolytic pharmacotherapies.

Identifying Metabolites of Meclonazepam by High-Resolution Mass Spectrometry Using Human Liver Microsomes, Hepatocytes, a Mouse Model, and Authentic Urine Samples

“…The adverse drug effects can be reversed by co-administration with flumazenil (9). As an anxiolytic, Ansseau et al (5) report a potency three times that of Svante Vikingsson and Ariane Wohlfarth contributed equally to this manuscript.…”

“…The pharmacology of meclonazepam has been investigated in clinical trials as an anxiolytic (5) and, interestingly, as a schistosomicidal drug to treat the parasitic worms Schistosoma haematobium and Schistosoma Mansori (6,7). Meclonazepam can successfully cure parasitic infections with a single dose of at least 0.3 mg/kg, but clinical tolerance was limited by severe adverse drug effects including drowsiness, dizziness, slurred speech, ataxia, muscle weakness, reduced mental alertness, and lateral nystagmus (7).…”

Experimentally promising antischistosomal drugs: a review of some drug candidates not reaching the clinical use

“…Ro 11-3128 (meclonazepam) is an anxiolytic benzodiazepine derivative (Ansseau et al 1985) whose antischistosomal properties were reported in the late 1970s (Pax et al 1978). It was considered as a putative drug lead according to the report of the Scientific Working Group on Schistosomiasis/ TDR/WHO (Cioli 2005).…”

Designer Benzodiazepines: A Review of Toxicology and Public Health Risks

“…Benzodiazepines (BZD), important forensic and clinical toxicology drugs, are widely prescribed for neurological and psychiatric disorders and are also highly abused [1][2][3]. Discovered in the mid-1950s, BZD were designed as pharmacotherapies for anxiety, panic attacks, sleep disorders and epilepsy, and they have been used as myorelaxants during surgical and orthopedic procedures [4,5]. BZD are positive allosteric modulators that enhance the binding affinity of the inotropic γ-aminobutyric acid-A receptor (GABA A ) for GABA, the major central nervous system (CNS) inhibitory neurotransmitter [6,7].…”