ENANTIOSELECTIVE EFFECTS OF LEVODROPROPIZINE AND DROPROPIZINE ON PSYCHOMOTOR FUNCTIONS IN NORMAL VOLUNTEERS - A PLACEBO-CONTROLLED, DOUBLE-BLIND COMPARATIVE-STUDY

Levodropropizine is the 1-isomer of dropropizine, a racemic drug widel y used as a cough suppressant. Compared with the racemate, levodroprop izine retains equal antitussive activity but exhibits considerably low er central nervous system (CNS) depressant effects in animal mode/s. I n order to assess whether the same differential pharmacodynamic profil e also applies to man, a double-blind placebo-controlled study was car ried out to investigate the effects of single oral doses (60 and 120 m g) of levodropropizine and dropropizine on subjective alertness (score d on visual analogue scales), general tolerability and psychomotor fun ction tests (cancellation, tapping, choice reaction times and critical flicker fusion frequency) in ten normal volunteers. Treatments were a dministered in random sequence at intervals of at least one week, eval uation procedures being carried out at times 0, 1, 2, 3, 4, 6 and 8 h after dosing, Following intake of a 60 mg levodropropizine dose, subje ctive effects and objective estimates of psychomotor function were sup erimposable to those recorded after placebo. There was a trend for 60 mg dropropizine and 120 mg levodropropizine to produce detrimental eff ects at occasional evaluations, although the changes associated with t hese treatments could not be differentiated from placebo on the basis of most subjective scores and psychomotor function tests. Conversely, administration of 120 mg dropropizine was consistently associated with subjective CNS impairment and with reduced performance (compared to b aseline) in recognition time, critical flicker fusion thresholds and p ossibly tapping rate, for up to three hours after dosing, These data a re consistent with evidence that racemic dropropizine adversely affect s central nervous system function to a greater extent compared with th e levo-isomer.