MCI-225, a novel thienopyrimidine analog, enhances attentional eye tracking in midpontine pretrigeminal preparation.

ABSTRACT

The effects of MCI-225, a novel psychoactive compound, and reference drugs on attention behavior were studied using visual stimulus induced vertical eye tracking movements in midpontine pretrigeminal (PTG) feline preparation. Surgery was performed under ether anesthesia and subsequently switched to nitrous oxide-fluothane which was discontinued only during experimental sessions. In addition xylocaine was locally injected. Vertical eye movements were monitored by electrooculogram (EOG) and a TV camera. To compare the effects of drugs on eye movement, numbers of spontaneous and tracking eye movements exceeding a present amplitude in EOG were counted before and during the visual stimulation, respectively. MCI-225 (1 and 3 mg/kg, i.v.) enhanced tracking movements dose-dependently without an increase in spontaneous eye movements. No or little change of the electrocorticogram (ECoG) was seen with 1 mg/kg MCI-225 and a slight increase in low voltage fast pattern was observed with 3 mg/kg, i.v.. On the other hand, tacrine (0.3 mg/kg, i.v.), physostigmine (0.03 mg/kg, i.v.) and methylphenidate (0.3 mg/kg, i.v.) enhanced both types of eye movement and induced ECoG arousal. Desipramine (3 mg/kg, i.v.) slightly increased spontaneous eye movement without affecting tracking movements. Piracetam (100 mg/kg, i.v.) decreased spontaneous eye movements only. These data clearly show that MCI-225 enhances attention to a moving object and suggest that MCI-225 could be useful in the treatment of attentional deficits and related cognitive dysfunctions in psychiatric disorders.