flunarizine and sabeluzole

The memory enhancing properties of sabeluzole nad flunarizine were evaluated in two experimental paradigms in male rats. First, we studied the protective action of both drugs against a chlordiazepoxide-induced impairment of habituation. Sabeluzole (5 or 25 mg/kg) or flunarizine (10 mg/kg) were administered sc 1 hr before and chlordiazepoxide (20 mg/kg) immediately after the acquisition session. In the retention session 72 hr later, chlordiazepoxide treated animals displayed higher locomotor and exploratory activities and this effect was blocked by pretreatment with sabeluzole or flunarizine. The results suggest that both drugs prevented amnesic effect of chlordiazepoxide. The second paradigm was the social memory test in which the time spent in social investigation behaviour toward a familiar or a novel juvenile conspecific was used to measure the duration of the memory that the animal forms of the juvenile. Sabeluzole (25 mg/kg) or flunarizine (3 mg/kg) were injected to the adults immediately after the initial exposure. Reexposure to the same or a novel juvenile was done 2 hr later. In contrast to controls, sabeluzole-treated animals showed a significant reduction in social investigation during reexposure to the same juvenile. Since there was no effect on investigation of a novel juvenile, results suggest that sabeluzole-treated rats are able to remember longer the individual characteristics of juvenile rats obtained through olfactory cues during a short social interaction. The time spent by adults treated with flunarizine in the investigation the same juvenile during reexposure was similar to that observed during the initial exposure. It means that flunarizine was ineffective in enhancing short-term olfactory memory.

Topics: Animals; Chlordiazepoxide; Flunarizine; Habituation, Psychophysiologic; Male; Memory; Piperidines; Rats; Thiazoles

The present paper reports two experiments is which an effect of sabeluzole and flunarizine upon behavioural consequences reflecting ischemic damage following cortical freezing lesions was evaluated in NMRI female mice. The parietal lesion was performed by applying a flat (2 mm in diameter) of a metal probe cooled to -75 degrees C on the exposed skull for 5 s. Flunarizine (15 mg/kg) was administered sc 1 hr before and 4 hr after performing the lesion and then, 1 mg/kg p.o. once daily for 14 days. Sabeluzole (5 mg/kg) was administered p.o. 1 hr before and 5 hr after performing the lesion and then, 5 mg/kg p.o. once daily for 14 days. Hole--board method was used to evaluate the exploratory head-dips activity of an animal in 5 sessions separated by 24 hr intervals during the postlesion testing from the 20th to the 24th day, i.e. from day 6 to 10 after finishing the treatment. The session lasted 5 min. In both experiments, the mean number of exploratory hole visits in lesioned female mice was significantly increased. Both flunarizine and sabeluzole reduced high hole exploration of lesioned mice to levels corresponding to those of the controls. Neither flunarizine nor sabeluzole affected significantly exploratory hole visit of control animals. Results showed that flunarizine as well as sabeluzole ameliorated behavioural disturbances reflecting the brain impairment induced through cortical freezing lesion. This effect is most probably related to the protective effect of both drugs against hypoxia induced in laboratory animals by several experimental procedures. The hole--board method seems to be suitable for the screening of compounds considered as cerebroprotective drugs.

Topics: Animals; Behavior, Animal; Cerebral Cortex; Female; Flunarizine; Freezing; Mice; Piperidines; Thiazoles

Unilateral photochemical infarcts were produced in the hind limb sensorimotor neocortex of 243 rats by intravenous injection of the fluorescein derivative Rose Bengal and focal illumination of the intact skull surface. Facial contact stimuli governed the degree and recovery rate of contralateral tactile/proprioceptive forelimb placing reactions. Contralateral forelimb placing recovered, whereas hind limb placing was resistant to recovery. Infarcted rats displayed marked recovery of spontaneous limb usage (beam traversing). However, deficits in isolated tactile/proprioceptive hind limb placing reactions endured. Posttreatment with the class IV calcium antagonist flunarizine after neocortical infarction protected sensorimotor function in a dose-dependent manner. This protective effect may be due to the peculiar ionic channel blocking profile of flunarizine. Scopolamine hydrobromide reinstated contralateral placing errors in infarcted rats at a dosage that did not affect neurologically intact rats. The cognitive enhancer sabeluzole, a novel benzothiazol derivative, dose-dependently blocked the anticholinergic-induced deterioration of a sensorimotor deficit in rats.

Topics: Animals; Calcium Channel Blockers; Cerebral Infarction; Flunarizine; Male; Movement; Nervous System; Physical Stimulation; Piperidines; Rats; Rats, Inbred Strains; Scopolamine; Somatosensory Cortex; Thiazoles