As described earlier, the disadvantages of the benzodiazepines include sedation, psychomotor and cognitive impairment, and withdrawal symptoms after long-term use. Increased understanding of benzodiazepine-receptor mechanisms suggested that compounds might be developed which are partial agonists and/or selective to some subtypes of receptor.(34) Such compounds would be less efficacious than full agonists but might have better adverse-effect profiles and less dependence potential, i.e. superior risk-benefit ratios.
One such compound, alpidem, was actually marketed in France but had to be withdrawn because of liver toxicity. Initial data suggested that it was somewhat less effective than a typical full benzodiazepine agonist but that it had a distinctly better side-effect profile. (36).
Abecarnil is a b-carboline which is anxiolytic in doses of 3 to 9 mg/day. However, efficacy has been difficult to demonstrate convincingly, although the side-effect profile does appear to resemble that of a comparator benzodiazepine.
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