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Laboratory of chemistry and pharmacology of drugs |
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Laboratory of chemistry and pharmacology of drugs |
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(812) 234 5447 Neurotransmitter systems exist in permanent interaction with each other, with reciprocal modulation. Conflicts in control often lead to unbalance among mediators and can be a reason for any disease. That is why the exploration of intra- and intersystem interactions of neuromediators is a very important task. Thus, complex influence upon M- and N-cholinergic mechanisms ensures successful correction of serotonin, norepinephrine and dopamine disbalance in brain diseases and visceral organs damages of neurogenic origin. New methods for treatment of such diseases as apathy-abulic syndrome in schizophrenia, hypertension and ulcerous diseases, bronchial asthma and damages of optic nerve are designed, based on a conception of the leading role of cholinergic system in organism. Use of selective blockers of parasympathetic ganglia allows to eliminate undesirable side central influence upon a target organ, but at the same time leaves a possibility for its self regulation, that greatly reduces side effects. Use of ganglia blockers with different structures allowed to design a topographical model of ion channel binding sites of N-cholinoreceptor and synthesize highly selective blockers for peripheral ganglia, 200 times more effective than hexonium.
Synthesis and conformational analyses of ligands for different subtypes of excitatory amino acids are performed in the lab. A new class of "super acid" agonists for NMDA-receptor - analogues of N-phthalamoyl-L-glutamic acid - is developed. A model for interaction between some "super acid" agonists with glutamate recognizing NMDA-receptor site is worked out. The proposed model allowed to synthesize a new set of selective ligands for NMDA-type receptors. These ligands are derivatives from heterocyclic dicarboxylic acids, in which manifestation of their blocker activity depends on lipophility of the molecules ( not on the distance between pharmacophore groups). A possibility for control the synaptic transmission mediated by excitatory amino acids allows correction of convulsive and degenerative brain disorders. |
The
Department is actively developing investigations in the field of
psychoneuroendocrinology. Disturbances in the hormonal status are known to
underlie the behavioral and cognitive deficiencies in aging, Alzheimer's
disease , the climacteric and premenstrual syndrome in women. Specific
features of memory and behavior were studied in behavioral tests in
animals with a deficiency and disbalance of thyroid hormones and estrogens
as well as in different phases of the estral cycle in female rats. On the
basis of investigations of the interaction between the endocrine and
neuromediator systems the preparations are being developed which combine
the properties of hormones (estrogen, androgen) and neurotropic agents
(agonist/antagonist of acetylcholine M1 receptors, 5-HT1A and 5-HT2A
serotonine, D1 and D2). Using the substances of this type will allow
simultaneous elimination of impairments both in the endocrine and
neuromediator systems thus preventing the formation of the "vicious"
circle. The molecular-pathogenetical investigations have shown impairments
of the neuroendocrine transmission (steroid, thyroid hormones, biogenic
amines and their metabolites), intranuclear transduction of the signal
(CK2-cascade) and expression of receptors (5-HT and 5-HT serotonine, 17b -estradiole)
in cognitive disorders associated with a deficiency of estrogens and
aging.