[NEUROCHEMICAL STUDY OF TROPOXIN EFFECTS ON THE CONTENT OF MONOAMINES AND ITS METABOLITES IN WISTAR RAT BRAIN STRUCTURES].

The influence of perspective anti-migraine drug tropoxin on the content of monoamines and related metabolites in Wistar rat brain structures, including frontal cortex (FC), hypothalamus, nucleus accumbens (NA), striatum, and hippocampus, has been studied using HPLC/ED technique. Tropoxin (10 mg/kg) induced a 30% decrease (p < 0.05) in dopamine (DA) level in FC as well as norepinephrine content in NA, while the concentrations of DA metabolites DOPAC and HVA in the hypothalamus were found to increase.

[STUDYING ANXIOLYTIC AND ANTIDEPRESSANT PROPERTIES OF 2,2,6,6-TETRAMETHYLPIPERIDONE DERIVATIVE.].

Neuropharmacological properties of LK-998 (3,4,5-trimethoxy-N'-(2,2,6,6-tetramethylpiperidin-4-yliden)benzohydrazide), a 2,2,6,6-tetramethylpiperidone de- rivative have been studied. LK-998 exhibited anxiolytic activity in doses of 10 and 20 mg/kg, significantly increasing the duration of animal staying of in open arms of the elevated plus maze as well as the number of arm entries. The efficiency of drug tested in a dose of 10 mg/kg was comparable with that of afobazole in a dose of 5 mg/kg.

[Cerebrovascular serotonin antagonists and agonist among tropan derivatives].

A series of new tropan derivatives have been synthesized and investigated, which can both weaken and potentiate the serotonin-induced cerebrovascular constrictory reactions. The compound LK-728 produces a pronounced antiserotonin cerebrovascular action comparable to that of tropoxin, but being superior to the reference drug in the effect duration. On the contrary, another tropan derivative LK-769 enhances the cerebrovascular response to serotonin.

[Interaction of tropoxin and its molecular fragments tropan and 3,4,5-trimethoxybenzoate with serotonin receptors of cortical neurons in the rat brain (a microionophoretic study)].

The effects of the antimigraine drug tropoxin and its main molecular fragments - tropan and 3,4,5-trimetoxybenzoate (TMB) - on the serotonin sensitivity of postsynaptic neuronal membrane in rat brain sensorimotor area has been studied using a microionophoretic (MIP) technique. All the three substances significantly reduce the excitatory neuronal response to serotonin, which is manifested by an increase in the rate of the spontaneous action potentials. With respect to the antiserotonin effect, the substances can be arranged in the following order: tropoxin > tropan > TMB.

[Tropoxin and cerebrovascular effects of serotonin].

The effect of serotonin on the brain blood supply was studied in rats before and after ischemic damage. The ischemic damage, induced by ligation of the middle meningeal artery, markedly enhanced the constrictor effect of serotonin on the brain vessels. Tropoxin, a 5HT2 receptor blocker, completely eliminated these cerebrovascular effects of serotonin.

[Tropoxin--a new serotonin antagonist and potential antimigraine agent].

The search for serotonin antagonists with cerebrovascular activity was conducted among newly synthesized aromatic and heteroaromatic ethers of tropinone oxim. One of these compounds, namely, hydrochloride-3(3,4,5-trimethoxybenzoiloxiimino-1)-8-methyl-8-a zab icyclo [3,2,1] octane, called tropoxin, prevented the development of serotonin-induced constriction of cerebral vessels in vitro and in vivo experiments. This effect was demonstrated also in experiments with oral administration of the drug.

[Central cholinolytic effect of tropane derivatives: structure-activity relationship].

The effect of two tropane derivatives on the electric neuronal activity in sensorimotor cortex was studied in rabbits using microiontophoretic method. Unlike atropine they lack aryl and hydroxyl, but possess morpholine and piperazine. The effects of both drugs were opposite to those of acetylcholine.

[Mechanism of the central effects of tropane].

The effect of tropan on exocellular-recorded electrical activity of brain sensorimotor cortical and ventrolateral thalamic neurons was studied in acute experiments on rabbits. Tropan was injected intravenously in a dose of 1-5 mg/kg and applied microiontophoretically to individual neurons. With both routes of administration tropan increased the frequency of spontaneous activity of the majority of cortical and thalamic neurons in the dose-dependent form.

[Effect of cocaine molecule fragments on the central nervous system].

The influence of ecgonine, tropine, tropinon, and some of their derivatives, propan, N-methylpyrrholidine, N-methylpiperidine on impulse summation in the central nervous system, conditioned reflex of avoidance, antagonism to hexenal, synergisim to cocaine and also their toxicity (LD50) have been studied under experimental conditions. As shown, benzoyl-ecgonine, ecgonine methyl ester, ecgonine, tropine, pseudotropine, carbomethoxytropinon, tropinon, tropine, tropan N-methylpyrrolidine, and N-methylpiperidine produced a pronounced stimulating effect on the central nervous system activity; in this respect they were similar to cocaine. The following conclusions were made: the substances whose molecules contained tropan structure or one of its fragments possess the central stimulating effect.