Influence of nootropic and antidepressive drugs on open field and running wheel behavior in spontaneously high and low active mice.

Mice differentiated by their running wheel activity into low and high active animals were chronically treated with the nootropics meclophenoxate, piracetam, vinpocetine, methylglucaminorotate, and the antidepressants lithium, desipramine, amitriptyline, and clomipramine. The influence of chronic drug treatment on running-wheel activity and open field locomotor behaviour was analyzed. Whereas with antidepressants rather sedative effects were observed in both activity types, the effects of nootropics were different in high and low active mice. Running-wheel scores increased in low active mice but decreased in high-active animals with an improvement in efficiency of locomotor behaviour in the open field of these mice after chronic nootropic treatment. In general, the effects of antidepressants seemed to be more uniform than those of the nootropics used.

Individual motor activity--relationships to dopaminergic responses.

Owing to motor activity mice were divided into two groups in a running-wheel test: low-active mice (LAM) and high-active mice (HAM). Locomotor activities in the running wheel and in glass boxes are compared. The HAM showed a more intensive explorative behavior than LAM and were also more responsive in terms of exogenous factors than LAM. In contrast, LAM showed higher locomotor activity than HAM after habituation. Analyzing the response of LAM and HAM to dopaminergic agonists such as apomorphine, bromocriptine, and amphetamine, the role of specific dopaminergic mechanisms for the two types is discussed. Although apomorphine mainly stimulated the climbing activity in HAM, bromocriptine (climbing activity) and amphetamine (locomotion) had stronger effects in LAM. Differences may be assumed between LAM and HAM concerning the nigrostriatal and/or mesolimbic dopaminergic mechanisms. On the one hand, climbing activity following apomorphine application accompanied by stereotypes may suggest a stronger activation of striatal dopaminergic mechanisms in HAM. On the other hand, climbing activity following bromocriptine accompanied by jumping behavior, as well as the stimulation of locomotion after amphetamine, suggests a more effective activation of mesolimbic dopaminergic structures in LAM.

Mexiletine in the treatment of diabetic neuropathy.

OBJECTIVE: To prove the efficacy of mexiletine in painful diabetic neuropathy. RESEARCH DESIGN AND METHODS: Treatment was provided in three dosages. For pain measurements, a VAS and McGill's verbal rating scale were chosen. Ninety-five patients were included in the study. RESULTS: A global assessment of the VAS among patients showed no differences between mexiletine treatment and placebo. The total evaluation (PRIT) of the McGill scale fell just below the level of significance. More specific exploratory evaluations of subclasses of the McGill scale, representing different degrees of pain, gave remarkable differences between mexiletine and placebo in sensory and miscellaneous items. In special subgroups, which were formed according to types and courses of complaints compiled at the beginning of this evaluation, the substantial advantages of the mexiletine treatment were shown with both the VAS and the McGill scale. CONCLUSIONS: Evidence strongly indicates that, in particular, those patients with stabbing or burning pain, heat sensations, or formication will benefit most by mexiletine therapy. Concerning the dosage, a medium regimen of 450 mg/day seems to be appropriate. With an increase in the antiarryhthmic dosage level, the efficacy does not rise proportionally. Mexiletine proved to be a safe therapy with negligible side effects at the medium dose range, even less than placebo; and remarkably, no cardiovascular side effects were noted. Further studies should avoid global assessments and pay more attention to the variety of complaints and quality of life.