The relationship between serum levels of metoprolol, hydroxymetoprolol and changes in psychomotor function as measured by standard reaction time and flash fusion frequency was studied. Blinded subjects were given placebo or 150 mg dose of metoprolol and crossed over on the next study day. Flash fusion frequency, reaction time, and serial blood levels of metoprolol and hydroxymetoprolol were collected. Oral dosing of metoprolol produced no significant changes in reaction time. However, significant decreases in flash fusion frequency were observed from 2 to 6 hours after the dose. Changes in flash fusion frequency were related to levels of metoprolol. Flash fusion frequency changes lagged behind the time course of metoprolol concentrations. The nadir of variance in the metoprolol plus hydroxymetoprolol concentration-effect relationship occurred when potency of hydroxymetoprolol was assumed to be 0.3 of metoprolol. These data suggest that the central nervous system actions of metoprolol are related to metoprolol serum levels and occur at low metoprolol concentrations. However, CNS effects of metoprolol do not intensify at high concentrations. Further CNS activity of hydroxymetoprolol may explain the lag seen in the relationship between concentration and CNS effect.
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