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Novel 2-aminoadamantane derivatives, specifically N-[2-(adamant-2-yl)-aminocarbonylmethyl]-N-(dialkylamino) alkylnitrobenzamides and their physiologically compatible salts, preferably the hydrochlorides, were synthesized and their...
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Novel 2-aminoadamantane derivatives, specifically N-[2-(adamant-2-yl)-aminocarbonylmethyl]-N-(dialkylamino) alkylnitrobenzamides and their physiologically compatible salts, preferably the hydrochlorides, were synthesized and their pharmacological properties were studied. The novel derivatives were found to have marked antiarrhythmic (antifibrillatory) activity in models of calcium chloride and aconitin arrhythmia. The relationship between the chemical structures of the substances synthesized here and their pharmacological activities was studied. The highest level of antiarrhythmic activity and the lowest toxicity were obtained with compound N-[2-(adamant-2-yl)aminocarbonylmethyl]-N-[3-diethylamino]propyl]-4-nitrobenzamide, which also had the advantage of a wider therapeutic ratio over known antiarrhythmic drugs of classes I, IV, and III (cardiocyclide).
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<abstract_text><p>The cerebrovascular and anti-ischemic effects of dopamine and synthetic docosahexaenoyldopamine (DHA-DA) and the GABA-DHA-DA conjugate (OXL1220) were compared and found to differ. Dopamine and DHA-DA increased bl...
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<abstract_text><p>The cerebrovascular and anti-ischemic effects of dopamine and synthetic docosahexaenoyldopamine (DHA-DA) and the GABA-DHA-DA conjugate (OXL1220) were compared and found to differ. Dopamine and DHA-DA increased blood flow in intact and ischemic brain that was associated with pronounced hypertensive reactions. The latter inhibited dopamine transporter with IC50 - 29 mu M but was practically inactive as a ligand for dopamine receptors. OXL1220 produced a selective vasodilating effect on blood flow in brain subjected to transient global ischemia. Only OXL1220 competed in vitro for specific binding sites of [H-3]-gabazine in rat-brain GABA(A)-receptors. Therefore, conjugation of a neuromediator (GABA) to the DHA-DA changed the dopaminergic activity of the compound to GABA-ergic with respect to vascular tone in ischemic brain.</p></abstract_text>
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New 5-hydroxyadamantan-2-one derivatives with heteroaromatic, aromatic, and aliphatic acids (nicotinic, succinic, p-chlorophenoxyacetic, 3,4,5-trimethoxybenzoic, and anisic) were synthesized. Their pharmacological properties were ...
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New 5-hydroxyadamantan-2-one derivatives with heteroaromatic, aromatic, and aliphatic acids (nicotinic, succinic, p-chlorophenoxyacetic, 3,4,5-trimethoxybenzoic, and anisic) were synthesized. Their pharmacological properties were studied to discover compounds with cerebrovascular anti-ischemic activity and without hypotensive activity. Esters of succinic acid and 5-hydroxyadamantan-2-one (diester Ia and monoester Ib, 100 mg/kg, i.v.) exhibited the most potent effect on cerebral circulation under ischemic conditions. They did not lower arterial blood pressure. The monoester was less toxic with LD50 740.0 (676.0 - 804.0) mg/kg. Analysis of the cerebrovascular effects of the succinate esters of 5-hydroxyadamantan-2-one using bicuculline revealed a GABA-ergic mechanism of action on cerebral vessels. However, radioligand analysis in vitro using the specific ligand [H-3]-SR 95531 found that these esters did not compete for rat-brain membrane GABA(A)-receptors. Thus, the monoester of succinic acid and 5-hydroxyadamantan-2-one possessed pronounced cerebrovascular anti-ischemic activity and did not produce hypotensive effects. The latter circumstance differentiated it from well-known drugs used in neurology (picamilon, Mexidol, nimodipine, cinnarizine, and Cavinton).
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Anew antimigraine drug - Tropoxin (3-(3,4,5-trimethoxybenzoyloxyimino)-8-methyl-8-azabicyclo[1-3]octane hydrochloride) - was developed and was found to prevent or significantly weaken the constrictor reactions of cerebral arteries...
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Anew antimigraine drug - Tropoxin (3-(3,4,5-trimethoxybenzoyloxyimino)-8-methyl-8-azabicyclo[1-3]octane hydrochloride) - was developed and was found to prevent or significantly weaken the constrictor reactions of cerebral arteries evoked by serotonin (5-HT) or the 5-HT2B/2C receptor agonist meta-chlorophenylpiperazine (m-CPP) in intact animals and in animals with ischemic brain damage. Tropoxin showed affinity for5-HT2 receptors in the brain and had antiaggregatory actions. It had no marked neurotropic properties and did not alter blood pressure responses to noradrenaline, acetylcholine, or histamine. Pilot clinical trials of Tropoxin provided evidence that it has high efficacy in the interictal treatment of frequent and severe migraine attacks.
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The cerebrovascular activity of 5-hydroxyadamantan-2-one succinic acid ester not only in ischemic brain injury but also in a more severe form of vascular damage to the body such as combined pathology (experimental myocardial infar...
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The cerebrovascular activity of 5-hydroxyadamantan-2-one succinic acid ester not only in ischemic brain injury but also in a more severe form of vascular damage to the body such as combined pathology (experimental myocardial infarction with subsequent global transient cerebral ischemia) was demonstrated experimentally in rats. The reference drug 5-hydroxyadamantan-2-one tested on combined vascular pathology more significantly lowered the level of arterial pressure, in contrast to experiments with cerebral ischemia. This entailed a decrease in the blood supply to the brain resulting from impaired autoregulation of cerebral circulation. Thus, the hypotensive effect of 5-hydroxyadamantan-2-one was transformed into a hypertensive effect by including a succinic acid moiety into its molecule. This effect was most pronounced when modeling combined vascular pathology of the brain and heart. The reference drug and to a much lesser extent 5-hydroxyadamantan-2-one succinic acid ester reduced the level of blood supply to the brain in experimental myocardial infarction.
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The cerebrovascular properties of 3,4,6,7,8,9-hexahydrodibenzo[b,d]furan-1(2H)-oneO-(4-cinnamoyl)oxime (C21H21NO3, GIZ-272) were studied. The ability of GIZ-272 to improve the brain blood supply in rats subjected to global transie...
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The cerebrovascular properties of 3,4,6,7,8,9-hexahydrodibenzo[b,d]furan-1(2H)-oneO-(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.
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We studied the effect of radioprotector indralin (B-190) alone or in combination with monizol on BP and HR in rabbits, reduction of blood supply and spleen weight in rats and (CBAxC57Bl/6)F1 hybrids mice, and on blood loss from a ...
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We studied the effect of radioprotector indralin (B-190) alone or in combination with monizol on BP and HR in rabbits, reduction of blood supply and spleen weight in rats and (CBAxC57Bl/6)F1 hybrids mice, and on blood loss from a wound on tip of the tail in mice. Being an alpha 1-adrenomimetic, indralin caused hypertensive reaction with the development of bradycardia, reduced blood supply and spleen weight, and sharply reduced blood loss from the wound. Monizol as nitrate reduced BP without affecting HR and reduced blood loss from the wound. Monizol administered prior to indralin eliminated radioprotector-induced hypertensive reaction, reduced bradycardia by more than 2 times, and attenuated the effect of indralin on spleen weight and blood loss from the wound by 1.6-1.8 times. Monizol administered after indralin had no effect on shifts in peripheral blood supply caused by the radioprotector.
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