EFFECTS OF THE ANTIMIGRAINE COMPOUND ZOLMITRIPTAN (ZOMIG) ON PSYCHOMOTOR PERFORMANCE ALONE AND IN COMBINATION WITH DIAZEPAM IN HEALTHY-VOLUNTEERS

Zolmitriptan (Zomig(TM)) is a 5HT(1B/1D) agonist which has the ability to cross the intact blood-brain barrier to access central as well as peripheral receptors. Because of the potential for central nervous sys tem side effects, this randomized, double-blind,placebo-controlled, 6- period crossover study evaluated the effects of 2.5 and 5 mg doses of zolmitriptan on psychomotor performance and investigated anp pharmacod ynamic or pharmacokinetic interaction with diazepam. Twelve healthy vo lunteers received the following ''treatments'' as single doses: zolmit riptan 2.5 mg, zolmitriptan 5 mg, diazepam 10 mg, zolmitriptan 2.5 mg + diazepam 10 mg, zolmitriptan 5 mg + diazepam 10 mg and placebo. Pre- dose and at 1, ii, 8, and 24 h post-dose, the following validated batt ery of psychomotor tests was performed: Bond-Lader visual analogue sca les (calmness, contentedness, and alertness factors), critical flicker fusion test, choice reaction time (recognition, motor, and total reac tion times), finger-tapping test, number cancellation test and digit s ymbol substitution test. Plasma concentrations of zolmitriptan, its ac tive metabolite, and diazepam and its active metabolites were measured at the same timepoints. Zolmitriptan 2.5 and 5 mg had no effect on ps ychomotor function when given alone. In contrast, diazepam 10 mg had p rofound effects, consistent with its sedative proper-ties, but there w as no synergism on concomitant administration of either dose of zolmit riptan. plasma concentrations of zolmitriptan, diazepam, and their res pective active metabolites were similar when the two drugs were given alone or in combination.