No abstract

It is known that natural isoquinoline alkaloids are widely used in pharmacology and have a variety of biological activities1. At the same time, synthetic analogs of isoquinoline alkaloids are of great interest, among which compounds have been identified that are promising agents that modulate the activity of the dopamine and serotonergic systems2,3, showing cardiprotective4 effect, antiproliferative5 and analgesic6 activity. Currently, in practical medicine, aspirin and anlagen are widely used as non-narcotic analgesics7. However, the low intensity of the analgesic effect, the lack of an analgesic effect in certain types of pain (thermal, mechanical, and other acute pain) and the large number of side effects caused by long-term use limits the scope of their application. The properties of 1-(4’-dimethylaminophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (3) have not been previously described in the scientific literature. The analgesic and anti-inflammatory activity of 1-(4'-dimethylaminophenyl)-6,7- dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (3) was studied under conditions of thermal (hot plate test) and chemical (vinegar writhing test) irritation, anti-inflammatory activity - on the model of acute inflammatory arthritis. As a result of the studies, it was found that the compound 1-(4'-dimethylaminophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline in various doses has an analgesic and anti-inflammatory effect. 1-(4'-Dimethylaminophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (3) showed a pronounced anti-inflammatory effect at a dose of 0.5 mg/kg, 3.3 times greater than the effect of diclofenac sodium. It has been shown that 1-(4’-dimethylaminophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (3) has a pronounced analgesic and anti-inflammatory activity and can be used in medical practice as a non-narcotic analgesic.

In studies, the alkaloid 1-(2-Chloro-4,5-methylenedioxyphenyl)-2-hydroxyethyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (N-14) had a negative inotropic effect on the activity of the papillary muscle contraction of the rat heart detected. Ca2+ ions from SR play an important role in the process of contraction of the heart muscle. With this in mind, the negative inotropic effect of the N-14 alkaloid was investigated with the modification of the accumulation processes of Ca2+ ions to SR. To clarify this, we examined the effects of the alkaloid being studied on SERCA2a and RyR2. To do this, the inhibitor of SERCA2a - cyclopiazonic acid (CPA) and RyR activator caffeine, which provide the accumulation of Ca2+ ions in SR, were used.