ACTION OF NEW 3-HYDROXYPYRIDINE DERIVATIVES WITH ANTI-NAUPATHIA PROPERTIES ON CENTRAL NEURONS.

Experiments with cats showed that microinjections into the lung of new 3-hydroxypyridine derivatives SK-119 and IBKhF-27 had a direct action on 50 and 84 % of medial vestibular nucleus (MVN) neurons respectively. The inhibitory response to the compounds was observed 6 and 25 times more frequently than exciting; inhibition by IBKhF-27 was observed 1.9 times more frequently than by SK-119. Also, microinjections of SK-1 19 and IBKhF-27 acted directly on 44 % and 81 % of cat's Purkinje cells, respectively. In case of Purkinje cells, the inhibitory reaction was seen 5.5 and 25 times oftener than exciting, respectively, and inhibition by IBKhF-27 occurred 2.1 times more frequently than by SK-119. Investigations of rat's cerebellum sections evidenced that 5 mM of IBKhF-27 inhibited population responses of Purkinje cells 95 1 3 %. In the presence of specific noncompetitive NMDA-receptor antagonist (MK-801, 100 pM) the depressive effect was annulled almost fully by 96 * 2 %. It follows that IBKhF-27 nearly entirely inhibits synaptic transmission from cerebellar parallel fibers to Purkinje cells, while MK-801 has a similarly strong anti-depression effect that testifies the involvement of the NMDA-receptor complex predominantly.

[STUDIES OF THE ANTIHYPOXIC AND ANTIAMNESTIC EFFECTS OF MELATONIN IN ANIMALS].

Experiments with mice showed that in a multitude of acute hypoxia models (normobaric hypoxic hypoxia with hypercapnia, hypobaric, hemic and histotaxic) the antihypoxic action of a single intra-abdominal dose of melatonin surpasses greatly amtisol, the standard antihypoxic agent. Single melatonin injection produced a strong antiamnestic action on various amnestic models (scopolamine-induced, acute normobaric hypoxia with hypercapnia, and a combination of extreme factors) which was much better than of pyracetame, a well-known nootropic (mind-stimulating) drug. Increase of the melatonin dose from 1 mg/kg to 20 mg/kg amplified both the antihypoxic and antiamnestic effects. Melatonin inhibited orthodromal population responses in surviving sections of rat's hippocampus (by 24 ± 3% at 2 mM; by 72 ± 6% at 5 mM). Besides, the inhibiting action of lusindol, a blocker of melatonin receptors MT1 and MT2--was virtually fully neutralized. Therefore, melatonin inhibits transmission within the Schaffer collateral--CA1 pyramidal neurons synapse by stimulation of melatonin receptors MT1 and MT2; higher melatonin concentrations (0.5 to 5 mM) enhance its effectiveness.

[VESTIBULAR AND THERMOPROTECTIVE PROPERTIES OF A NEW ACTOPROTECTOR].

In experiments with rats, a new 3-hydroxypyridine (3-HP) derivative--2-ethyl-6-methyl-3-hydroxypyridine L-asparaginate (30 mg/kg)--exhibited a strong vestibuloprotective effect which was better than of promethazine (50 mg/kg), a well-known vestibuloprotector Besides the new actoprotector was competitive with another 3-HP derivative, namely, mexidol (ethyl-methyl-hydroxypyridine succinate) (100 mg/kg). Moreover, a distinct thermoprotective effect of 2-ethyl-6-methyl-3-hydroxypyridine L-asparaginate (30 mg/kg) in mice was not worse than that of mexidol or metaprot (ethylthiobenzimidasol, former name bimethy), an actoprotector with good thermoprotective properties. To conclude, owing to the membrane-protective and antioxidative qualities, the vestibuloprotective and thermoprotective properties of 2-ethyl-6-methyl-3-hydroxypyridine L-asparaginate are better or competitive with the reference preparations.