Analysis of the Cerebrovascular Effect of a Dibenzofuran Oxime Derivative
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Pharmaceutical Chemistry Journal, Vol. 54, No. 6, September, 2020 (Russian Original Vol. 54, No. 6, June, 2020)
ANALYSIS OF THE CEREBROVASCULAR EFFECT OF A DIBENZOFURAN OXIME DERIVATIVE R. S. Mirzoyan,1 T. S. Gan’shina,1 I. N. Kurdyumov,1 E. V. Kurza,1 D. V. Maslennikov,1 A. I. Turilova,1 and L. M. Zhmurenko1 Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 54, No. 6, pp. 20 – 23, June, 2020.
Original article submitted March 4, 2020. The cerebrovascular properties of 3,4,6,7,8,9-hexahydrodibenzo[b,d]furan-1(2H)-one O-(4-cinnamoyl)oxime (C21H21NO3, GIZ-272) were studied. The ability of GIZ-272 to improve the brain blood supply in rats subjected to global transient ischemia and to a lesser extent in animals with a hemorrhagic stroke model was established. The compound had cerebrovascular anti-ischemic activity comparable to that of Mexidol and a duration of action longer than that of nimodipine. It is important to note that GIZ-272 did not cause a decrease in blood pressure and was superior to both Mexidol and nimodipine in this respect. An analysis of the cerebrovascular effect of GIZ-272 using bicucullin indicated that the GABA-ergic system of cerebral vessels participated in implementation of the anti-ischemic effect of the compound. Keywords: dibenzofuran oxime derivative; 3,4,6,7,8,9-hexahydrodibenzo[b,d]furan-1(2H)-one O-(4-cinnamoyl)oxime (C21H21NO3); cerebral circulation; cerebral ischemia; hemorrhagic stroke model; bicucullin; GABAA-receptor.
Cerebral vascular diseases are one of the leading causes of morbidity and invalidism among the world’s population [1]. Known cerebrovascular drugs are not always highly effective so that new agents for treating cerebral circulatory disorders must be discovered and studied. The basic strategy for treating patients with cerebrovascular disorders is to restore the blood supply to the damaged brain region for rapid influx of oxygen and glucose to brain tissue. Therefore, the ability to enhance the cerebral blood supply plays a decisive role in the anti-ischemic activity of drugs [2]. Previously, the new dibenzofuran oxime derivative 3,4,6,7,8,9-hexahydrodibenzo[b,d]furan-1(2H)-one O-(4-cinnamoyl)oxime (C21H21NO3, GIZ-272) was synthesized and studied pharmacologically in our Institute. It possessed potent anticonvulsant activity by eliminating primary generalized convulsions in basic antagonism tests with maximum electric shock and corazole. The compound also had antihypoxic activity, protected rats from death in a global cerebral ischemia model, improved brain blood supply, and decreased the manifestation of neurological deficiencies and disrup1
tions of exploratory activity [3, 4]. The literature indicates that several antiepileptic drugs, e.g., levetiracetam, topiramate, and lamotrigine, possess neuroprotective activity due apparently to the similar pathogenesis of epilepsy and ischemia (glutamate neurotoxicity, oxidative stress, intracellular Ca accumulation, inflammatory cytokines). Therefore, the goal of the present research was to study systematically the
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