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(R)) - a quinoxaline derived from isoquinolin e, the basic structure of papaverine, originally developed as a spasmo lytic drug which may, however, exert central effects die to an unspeci fic calcium channel blocking action and glutamate antagonism - were in vestigated 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 ca roverine intravenously, 40 and 80 mg caroverine orally as well as plac ebo. EEG recordings, psychometric and psychophysiological tests, as we ll as evaluation of pulse, blood pressure and side-effects were carrie d out at 0, 1, 2, 4, 6 and 8 h. Multivariate analysis of EEG mapping d ata demonstrated that caroverine exerted a significant action on human blain function, as compared with placebo, at all given dosages, as ea rly as in the Ist and as late as in the 8th hour after both intravenou s and oral administration during resting (R-EEG) and vigilance-control led recording (V-EEG). Subsequent univariate analyses revealed, howeve r differential effects of caroverine - dependent on recording conditio ns and doses. In the resting condition, an increase of absolute and re lative delta and theta power, a decrease of alpha and beta power and a slowing of the centroid of the delta and theta activity occurred, ref lecting sedative action. The latter was slightly time- and dose-depend ent (more sedation in earlier hours after higher doses). However, in t he vigilance-controlled EEG, a dose-dependent decrease of delta and th eta power; an increase of alpha power and an acceleration of the centr oid of the delta and theta suggested vigilance-promoting effects, whic h were more pronounced in the later than earlier hours. Psychometric i nvestigations conformed these differential central effects. In regard to the noopsyche, an improvement was noted 6 h after the lowest oral c lose. In the thymopsyche, a deterioration occurred after all doses exc ept the highest oral dose, suggesting sedation. The latter was also se en after all active compounds as a trend in psychophysiological variab les. The drug was well tolerated.