Effects of azaleptine and its new derivative seleptine on spontaneous EEG activity and the activation reaction in rabbits

Abstract

The neuroleptic azaleptine and its new derivative seleptine with anticonvulsive properties were examined in a chronic experiment on rabbits for their comparative effects on the spontaneous electroencephalogram (EEG) and the activation reaction in the sensorimotor cortex and dorsal hippocampus. Azaleptine induced synchronization of electroencephalographic activity in all frequency ranges of both cortical and hippocampal EEGs, while seleptine induced desynchronization in the. cortical EEG and synchronization in the 5, 0, and I~ ranges of the hippocampal EEG. Both compounds prevented the activation or altered its pattern, leading to a decrease in the power of the 13 range rather than increasing it as is normally observed.Key Words: azaleptine; seleptine; neuroleptics; anticonvulsants; total electroencephalogram; activation reaction, which has been successfully used in medical practice, is a typical neuroleptic with a unique neuropharmacological profile [4,8]. Its new structural analog seleptine (8-chloro-11-(4-methyl-1-piperazinyl)-5-acetylaminodibenzo-[b,e][1,4]-diazepine) is regarded as a potential anticonvulsant with possible psychotropic properties.In this study on rabbits, we compared the effects of the two compounds on spontaneous electric activity of the sensorimotor cortex and dorsal hippocampus as a test for alterations in the general excitability of the brain and in the functional status of neurotransmitter systems. MATERIALS AND METHODSThis chronic experiment was carried out on rabbits (bodyweight 2.3-3.5 kg), 6 animals in each group, implanted stereotaxicaUy with bipolar nichrome electrodes under Nembutal anesthesia (30 rag/ kg after Aminazine [chlorpromazine] administration). The recording electrodes were implanted into the sensorimotor area of the neocortex (AP 2-3; L 2; H 2) and into area CA3 of the dorsal hippocampus (AP 5.5-7; L 5.2-6.5; H 3.5), the stimulating electrodes were implanted into the mesencephalic part of the reticular formation (nucleus cuneiformis, pars dorsalis; AP 13.5; L 2.4; H 7), while the indifferent electrodes were placed in the nasal bone and over the visual cortex in the occipital bone. Tests were started 5-7 days postimplantation.The total electroencephalogram (EEG) was recorded bipolarly in nonrigidly fixed animals in a shielded soundproof darkened chamber. The EEG