Attenuation of response to mental stress in patients with essential tremor treated with metoprolol.

The response to mental stress in patients with benign essential tremor is an exaggeration of the resting tremor. We have studied the ability of metoprolol tartrate to attenuate specifically the tremorgenic response to mental stress in five patients with essential tremor who were each studied on four occasions. Treatment regimens consisted of 0-, 25-, 50-, and 75-mg doses of metoprolol tartrate, given twice daily for seven- to ten-day periods. Tremor was measured while patients were resting comfortably and then again following mental stress over eight-hour study periods. During the baseline study period, the investigational mental stress consistently exaggerated tremor in each patient. Metoprolol treatment reduced both the resting tremor and tremor following mental activity, but the drug-induced change in the response to mental stress was more pronounced than the drug-induced reduction in resting tremor. The ability of metoprolol to blunt the response to mental stress was associated with serum concentrations of the drug. The time courses of metoprolol serum concentrations were similar to the time course of metoprolol's ability to blunt the response to mental stress. Metoprolol possesses the ability to blunt the tremorgenic response to mental stress in patients with essential tremor, but the duration of this effect lasts less than seven hours after administration of a dose.

The relationship between serum concentrations and central nervous system actions of metoprolol.

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.