Benzodiazepines and sleep induction: A possible role of potential-dependent calcium flux in neurons

The induction of sleep by BZs has pharmacological characteristics consistent with mediation through the central BZ receptor. While the most strongly supported effector mechanism for the receptor-mediated actions of BZs is a chloride channel associated with the BZ receptor complex, recent evidence suggests an additional effect of BZs on depolarization-dependent calcium ion flux (Paul et al., 1982; Mendelson et al., 1984b). The possibility arises, then, that a subclass of BZ receptor is associated with a calcium channel, and that some of the actions of BZs are mediated through an action at this site. Further research is necessary to clarify the relation between subtype of BZ receptor and BZ facilitation of calcium flux. Behavioral data indicate that while nifedipine blocked the effects of flurazepam in shortening the time until the onset of sleep, a larger dose was ineffective in blocking the anticonvulsant effects of flurazepam. Thus, it may be that dihydropyridine calcium channel blockers are relatively specific in influencing BZ-shortened latency to sleep onset and not other behavioral measures. In contrast, chloride channel blockers may be more potent in influencing other behavioral effects of BZs. The demonstration of a pharmacological differentiation between various behavioral effects of BZs would open the door to the possibility of development of BZ-like drugs having novel behavioral specificities.