METHOD FOR RAPID SAFETY ASSESSMENT OF Κ-OPIOID RECEPTOR AGONISTS Russian patent published in 2023 - IPC G01N33/00 G01N25/00 A61B5/01 

FIELD: painkillers.

SUBSTANCE: invention relates to methods for preclinical studies of the safety of painkillers from the class of agonists κ-opioid receptors and can be used in the development of new painkillers. The method involves administering the test substances to white sexually mature male rats in 5 doses, six animals each, observing eight symptoms of side effects, and conducting the Hot Plate primary observation test at a plate temperature of 50°C. If a manifestation in a complex of six specific symptoms of side effects is registered, namely hypolocomotion, spreading, protrusion, vocalization, polyuria, hypothermia, as well as an analgesic effect on a hot plate simultaneously with the absence of two symptoms, Straube reactions and catalepsy, a conclusion is made that the substance belongs exclusively for the class of κ-opioid antagonists. The calculation of the average analgesic dose is carried out, as well as the calculation of the average toxic dose according to the side effect symptom with the lowest dose value, the calculation of the breadth of the therapeutic effect as a quotient from dividing the average toxic dose by the average analgesic dose. The therapeutic index is also calculated as the quotient of the toxic dose causing symptoms in 25% of the animals divided by the analgesic dose causing the effect in 75% of the animals. Agonists are considered safe κ-opioid receptors with values of the range of therapeutic action and therapeutic index greater than those of the reference drug butorphanol.

EFFECT: quick safety assessment of symptoms that are specific for agonists of κ-opioid receptors, simple to perform, easily reproducible, requiring no long-term adaptation of animals to experimental conditions and using special expensive equipment, reduced number of experimental animals participating in the experiment.

4 cl, 3 dwg, 1 tbl, 5 ex