Discoveries in molecular ...

Discoveries in molecular biology have enhanced our understanding of the fundamental mechanisms of hypnotic effect. Basic biological substratum of hypnotic drugs is рецепторныйГАМКбензодиазепиновый Cl supramolecular complex, located on the membranes of neurons, which regulates cell stimulation and operated primarily as a valve chloride channel. To date, revealed the heterogeneity of benzodiazepine (BZ) receptor and determined the localization and function of its main subtypes w1, w2 and w5. Subtype w1 (BZ) is located predominantly in the cortical and subcortical areas and is responsible for the appearance of actual hypnotic action, whereas subtypes w2 and w5 are localized mainly in the spinal cord and peripheral tissues and are associated with the emergence of a host of other effects (muscle relaxant, anticonvulsive, etc.) . Three generations of hypnotics are different varying degrees of selectivity of the neurochemical actions of the various components of ГАМКбензодиазепиновогохлорного complex. Moreover, the increase of selectivity of action corresponds to an increase of security and portability of their application. The lowest selectivity are characterized by first-generation hypnotics that now practically not applied in the treatment of insomnia. For example, barbiturates, influencing the chlorine channel, causing an undifferentiated process of braking, which can be compared with undifferentiated shocks therapies psychotic states, and cause a forced sleep, similar in characteristics to the narcotic. Characterized by greater selectivity of benzodiazepine derivatives, the main mechanism of action which is associated with activation of all types of benzodiazepine receptors, which increases the affinity of GABA to GAMKretseptoru and as a result also leads to an increase in the number of open channels of chlorine. The latest generation of hypnotics differs the greatest degree of selectivity, the biological substrate ? ? actions are subtypes of w1 and w2 of the benzodiazepine receptor, which in accordance with modern concepts directly related to the emergence of pure hypnotic effect. Pharmacodynamic differences between the three generations of hypnotics related differences in the sequence of appearance of their pharmacological effects at escalating dosages. For example, barbiturates, characterized by the simultaneous appearance of a variety of effects (hypnotic, anticonvulsive, muscle relaxant, anxiolytic, amnestic) at sufficiently low doses. Benzodiazepines, in contrast to the first generation of drugs, are drugs with a well-defined dose-related effects: the hypnotic effect of the drug occurs after the anxiolytic at escalating dosages of medications. A characteristic feature of the hypnotics of third generation is the appearance of first gipnosedativnogo action, and in a subsequent increase in dosage of drugs and other tranquilizing effects.