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Neurophysiological effects of heptastigmine in aged rats
Pharmacological Research, Vol. 26, Supplement 1, 1992
153
NEUROPHYSIOLOGICALEFFECTSOF HEPTASTIGMINEIN AGED RATS. M.T. Tebano, L. Bortot*, P. Capriani, C. Cutrufo*, M. Luzi, M. Marta* *, M. Pomponi**, S. Palazzesi,A. Loizzo Istituto Superiore di Sanita’, Roma; *Menarini Sud, Pomezia (RM); **Universita’ Cattolica SacroCuore, Roma. The interest about the cholinergic systemin the regulation of EEG activity was risen by studies showing a decreasein central cholinergic transmissionand the slowing of EEG activity in patients with Alzheimer disease.We studied the effects induced by a new anticholinesterase agent, the “Heptastigmine”(He-Phy), on the EEG power analysisand on flash- visual evoked potentials (VEPs) in aged rats (24-28 months) on a hypocaloric diet. Wistar Kyoto rats were cronically implantedwith four cortical electrodes.The EEG signal recorded on tape was bandpass filtered and power spectra analysis was performed. Approximately 70-90% of power spectrum is found within delta (OS-4 Hz) and theta (4.25-7 Hz) frequency bands. The doses tested of He-Phy (0.5 and 0.25 mg/kg i.p.) produced, one hour after the treatment, a dosedependentincreasein the power of total spectrumand of theta band. In another seriesof experimentscortical VEPswere recordedand the latency and peak-to-peak amplitude of major peaks were measured.After the two doses administeredwe observed an increasein amplitudeand a decreasein the latencyof the slow componentof VEPs. These preliminary data suggestthe possibletherapeuticuse of the He-Phy in the treatment of central cholinergic systemalterations.
PRELIMINARY RESULTS OF SELEGILINE TREATMENTOF VISUOSPATIAL MEMORYDEFICITS IN ALZHEIMER'S DISEASE Giancarlo Finali, Massimo Piccirilli, Gian Luigi Piccinin Department of Neurology, University of Perugia, Italy. The severity of verbal memory disorders exhibited by patients with Alzheimer's disease (AD) overshadows the presence of other cognitive deficiences. Intellectual deficits, however, include specific impairments in visuospatial functions. for nonverbal The study of memory and learning material is important since linguistic abilities are often affected in AD and such abnormalities may confound mnemonic dysfunction. Visuospatially mediated memory tasks were therefore chosen to investigate the cognitive effects of selegiline, a selective MAO-B inhibitor, in 28 patients (mean age,61.8 yrs) with diagnosis of AD, according to DSM-III-R and NINCDS-ADRDA clinical criteria, and with a mild to moderate mental deterioration. In a double blind randomized crossover versus placebo trial lasting 6 months, selegiline was tested for visuospatial memory activity. Neuropsychological performances was assessed by means of the Barbizet-Cany test, which provides a series of indicators of visuospatial memory functioning: total retrieval, short-term and long-term retrieval, spatial learning, learning shape, forgetting. Preliminary analysis of the results indicates an improvement of some measures of visuospatial mnesic processes.
153
NEUROPHYSIOLOGICALEFFECTSOF HEPTASTIGMINEIN AGED RATS. M.T. Tebano, L. Bortot*, P. Capriani, C. Cutrufo*, M. Luzi, M. Marta* *, M. Pomponi**, S. Palazzesi,A. Loizzo Istituto Superiore di Sanita’, Roma; *Menarini Sud, Pomezia (RM); **Universita’ Cattolica SacroCuore, Roma. The interest about the cholinergic systemin the regulation of EEG activity was risen by studies showing a decreasein central cholinergic transmissionand the slowing of EEG activity in patients with Alzheimer disease.We studied the effects induced by a new anticholinesterase agent, the “Heptastigmine”(He-Phy), on the EEG power analysisand on flash- visual evoked potentials (VEPs) in aged rats (24-28 months) on a hypocaloric diet. Wistar Kyoto rats were cronically implantedwith four cortical electrodes.The EEG signal recorded on tape was bandpass filtered and power spectra analysis was performed. Approximately 70-90% of power spectrum is found within delta (OS-4 Hz) and theta (4.25-7 Hz) frequency bands. The doses tested of He-Phy (0.5 and 0.25 mg/kg i.p.) produced, one hour after the treatment, a dosedependentincreasein the power of total spectrumand of theta band. In another seriesof experimentscortical VEPswere recordedand the latency and peak-to-peak amplitude of major peaks were measured.After the two doses administeredwe observed an increasein amplitudeand a decreasein the latencyof the slow componentof VEPs. These preliminary data suggestthe possibletherapeuticuse of the He-Phy in the treatment of central cholinergic systemalterations.
PRELIMINARY RESULTS OF SELEGILINE TREATMENTOF VISUOSPATIAL MEMORYDEFICITS IN ALZHEIMER'S DISEASE Giancarlo Finali, Massimo Piccirilli, Gian Luigi Piccinin Department of Neurology, University of Perugia, Italy. The severity of verbal memory disorders exhibited by patients with Alzheimer's disease (AD) overshadows the presence of other cognitive deficiences. Intellectual deficits, however, include specific impairments in visuospatial functions. for nonverbal The study of memory and learning material is important since linguistic abilities are often affected in AD and such abnormalities may confound mnemonic dysfunction. Visuospatially mediated memory tasks were therefore chosen to investigate the cognitive effects of selegiline, a selective MAO-B inhibitor, in 28 patients (mean age,61.8 yrs) with diagnosis of AD, according to DSM-III-R and NINCDS-ADRDA clinical criteria, and with a mild to moderate mental deterioration. In a double blind randomized crossover versus placebo trial lasting 6 months, selegiline was tested for visuospatial memory activity. Neuropsychological performances was assessed by means of the Barbizet-Cany test, which provides a series of indicators of visuospatial memory functioning: total retrieval, short-term and long-term retrieval, spatial learning, learning shape, forgetting. Preliminary analysis of the results indicates an improvement of some measures of visuospatial mnesic processes.