Acute central effects of the calcium channel blocker and antiglutamatergic drug caroverine. Double-blind, placebo-controlled, EEG mapping and psychometric studies after intravenous and oral administration.

In a double-blind, placebo-controlled study, the effects of caroverine (CAS 23465-76-1, Spasmium)--a quinoxaline derived from isoquinoline, the basic structure of papaverine, originally developed as a spasmolytic drug which may, however, exert central effects due to an unspecific calcium channel blocking action and glutamate antagonism--were investigated utilizing EEG-mapping, psychometric and psychophysiological measures. Fifteen healthy volunteers (8 males and 7 females), aged 20-35 years, received randomized and at weekly intervals 40 and 80 mg caroverine intravenously, 40 and 80 mg caroverine orally, as well as placebo. EEG recordings, psychometric and psychophysiological tests, as well as evaluation of pulse, blood pressure and side-effects were carried out at 0, 1, 2, 4, 6 and 8 h. Multivariate analysis of EEG mapping data demonstrated that caroverine exerted a significant action on human brain function, as compared with placebo, at all given dosages, as early as in the 1st and as late as in the 8th hour after both intravenous and oral administration during resting (R-EEG) and vigilance-controlled recording (V-EEG). Subsequent univariate analyses revealed, however, differential effects of caroverine--dependent on recording conditions and doses. In the resting condition, an increase of absolute and relative delta and theta power, a decrease of alpha and beta power and a slowing of the centroid of the delta and theta activity occurred, reflecting sedative action. The latter was slightly time- and dose-dependent (more sedation in earlier hours after higher doses). However, in the vigilance-controlled EEG, a dose-dependent decrease of delta and theta power, an increase of alpha power and an acceleration of the centroid of the delta and theta suggested vigilance-promoting effects, which were more pronounced in the later than earlier hours. Psychometric investigations confirmed these differential central effects. In regard to the noopsyche, an improvement was noted 6 h after the lowest oral dose. In the thymopsyche, a deterioration occurred after all doses except the highest oral dose, suggesting sedation. The latter was also seen after all active compounds as a trend in psychophysiological variables. The drug was well tolerated.