Effects of the antimigraine compound zolmitriptan ('Zomig') on psychomotor performance alone and in combination with diazepam in healthy volunteers.
Zolmitriptan (Zomig) is a 5HT1B/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 system 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 any pharmacodynamic or pharmacokinetic interaction with diazepam. Twelve healthy volunteers received the following "treatments" as single doses: zolmitriptan 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, 4, 8, and 24 h post-dose, the following validated battery of psychomotor tests was performed: Bond-Lader visual analogue scales (calmness, contentedness, and alertness factors), critical flicker fusion test, choice reaction time (recognition, motor, and total reaction times), finger-tapping test, number cancellation test and digit symbol substitution test. Plasma concentrations of zolmitriptan, its active metabolite, and diazepam and its active metabolites were measured at the same timepoints. Zolmitriptan 2.5 and 5 mg had no effect on psychomotor function when given alone. In contrast, diazepam 10 mg had profound effects, consistent with its sedative properties, but there was no synergism on concomitant administration of either dose of zolmitriptan. Plasma concentrations of zolmitriptan, diazepam, and their respective active metabolites were similar when the two drugs were given alone or in combination.
Dixon
R
R
Clinical Pharmacology Unit and Drug Kinetics, Zeneca Pharmaceuticals, Macclesfield, Cheshire, UK. Ruth.Dixon@ALDERLEY.ZENECA.com
Hughes
A M
AM
Nairn
K
K
Sellers
M
M
Kemp
J V
JV
Yates
R A
RA
D000328:Adult; D018592:Cross-Over Studies; D003975:Diazepam / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010080:Oxazoles / Q000097:blood / Q000627:therapeutic use*; D023303:Oxazolidinones; D011594:Psychometrics; D011597:Psychomotor Performance / Q000187:drug effects*; D012016:Reference Values; D017366:Serotonin Receptor Agonists / Q000097:blood / Q000627:therapeutic use*; D014363:Tryptamines
D006993:Hypnotics and Sedatives; D010080:Oxazoles; D023303:Oxazolidinones; D017366:Serotonin Receptor Agonists; D014363:Tryptamines; C089750:zolmitriptan; D003975:Diazepam