Psychomotor-stimulant effects of 3-isobutyl-1-methylxanthine: comparison with caffeine and 7-(2-chloroethyl) theophylline.

The behavioral effects of 3-isobutyl-1-methylxanthine (IBMX) were compared with those of caffeine and 7-(2-chloroethyl) theophylline (7-CET) in squirrel monkeys under a multiple schedule of reinforcement in which fixed-interval responding was maintained alternately by presentation of food and presentation of electric shock. All three drugs produced dose-related increases in response rate in both components of the multiple schedule. Thus, although IBMX generally lacks psychomotor-stimulant effects in rodents, it had behavioral effects in squirrel monkeys that were qualitatively similar to those of caffeine. Based on the average ED50 values, IBMX was 5-7 times more potent than caffeine and 7-CET was twice as potent as caffeine in the two schedule components. This potency relation corresponds well with those observed in radioligand binding assays for central adenosine receptors and is consistent with the view that the psychomotor-stimulant effects of methylxanthines are linked to their antagonistic actions at the adenosine-receptor level. There was no obvious correspondence between the capacity of the methylxanthines to increase response rate and their capacity to inhibit phosphodiesterase activity.