From our point of view, watch ...

Causes of central and less peripheral [18] mechanism for tolerance to morphine was considered reducing the number of opiate receptor binding sites, reducing their affinity for agonists or an increase in affinity for the antagonist, but this was not confirmed in further studies [3] . At the same time, the morphine-tolerant animals was found low levels of endogenous opioids in brain structures, pituitary and plasma [15]. We have previously stated [5] and confirmed by neurochemical studies [6] hypothesis about the role of enkephalinase A in the formation of states morphine tolerance / dependence, and also proved the feasibility of using small doses of naloxone (in which it behaves as an inhibitor of enkephalinase A) for the suppression of tolerance and then depending on the models of experimental opioid addiction [7]. According to our hypothesis, chronic administration of morphine occurs a gradual increase in enkephalinase activity, as the response of the organism to the constant improvement of the selection of endogenous opioids as a result of these chronic externalities, which leads to an increase in their rate of deactivation, and thus to the disappearance of its analgesic effect, ie e. to the development of the state of tolerance. Chronic administration of naloxone to enkephalinase inhibitory doses causes a gradual decrease in activity of the latter, which leads to increased levels of active endogenous opioids and the manifestation of the analgesic effect. In recent years, will have enough work overseas supporting our data on the possible suppression of low-dose naloxone state of tolerance / dependence. However, in these studies the effect obtained is described as a paradox for the opioid antagonist. Describing this as a paradoxical effect, the authors nevertheless recommend the use of small doses of naloxone (naltrexone) in the clinic to increase the antinociceptive effect and lower tolerance / dependence on morphine. In Grain S. and Shen K.F. [11] described the results of preclinical and clinical trials of a complex of extremely low doses of naloxone or nalmefene with morphine, which found a significant increase in antinociceptive properties of morphine and simultaneous reduction of opiate addiction as a result of this combination of agonist with low doses of naloxone. From our point of view, these authors observed a paradoxical effect of opioid antagonist, completely fits in the view expressed our view on the effect of it in small doses as an inhibitor of enkephalinase. Our data served as the fundamental rationale for the study of neurochemical and physiological parameters in order to develop methods of pathogenetic therapy of patients with heroin addiction. The methodology and results in order to determine the criteria for inclusion in the experiment contingent juvenile heroin addicts were examined 50 patients admitted for inpatient treatment at the state of dependence on heroin, according to the criteria of the International Classification of Diseases, 1910 revision.