Anticonvulsant Potential of 1-Aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolines: Insights from Strychnine and Nicotine Models in In Vivo and In Silico Studies

Anticonvulsant Potential of 1-Aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolines: Insights from Strychnine and Nicotine Models in In Vivo and In Silico Studies

Azamatov, A.A.; Mamadalieva, N.Z.; Mandour, A.A.; Zhurakulov, S.N.; Aytmuratova, U.K.; Vinogradova, V.I.; Jalilov, F.S.; Tursunkhodzhaeva, F.M. Anticonvulsant Potential of 1-Aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolines: Insights from Strychnine and Nicotine Models in In Vivo and In Silico Studies. Pharmaceuticals 2025, 18, 1350. https://doi.org/10.3390/ph18091350

Uzbek Patent IAP 07567 «Antidote to strychnine and anticonvulsant remedy»

According to data as of the beginning of 2026, more than 50 million people suffer from epilepsy. This makes it one of the most common neurological diseases in the world.

The Department of Pharmacology and Toxicology of the Institute of the Chemistry of Plant Substances, Academy of Sciences of Uzbekistan is conducting research on the anticonvulsant activity of natural and synthetic compounds. As a part of this research, it has been studied whether derivatives of 1,2,3,4-tetrahydroisoquinoline can exhibit anticonvulsant properties. For this purpose, a series of 32 derivatives was studied on experimental models of nicotine and strychnine convulsions, the structure-activity relationship was analyzed, and the most active compounds were selected. The authors conducted pharmacophore analysis in silico, as well as molecular docking targeting AMPA receptors.

As a result of the conducted research, two candidate substances were identified that showed the highest activity against strychnine-induced convulsions, and 11 substances that showed high efficacy in the nicotine-induced convulsion model. Docking results using AMPA (PDB ID: 1FTL) showed comparable binding interactions for the most compounds, with a range of interaction energy (−)C-Docker 33.82–45.41 kcal/mol compared to the ligand (41.60 kcal/mol). The main pharmacophoric characteristics necessary for anticonvulsant activity were identified. In addition, an ADMET predictive study was conducted to assess the pharmacokinetic and toxicological profiles of the compounds. Thus, it was shown that among the derivatives of 1,2,3,4-tetrahydroisoquinoline, there are compounds that can be used to develop anticonvulsant drugs, including those for pharmacoresistant epilepsy.

https://t.me/uzicpsuz/732