Folia Medica 62(3): 532-538, doi: 10.3897/folmed.62.e47844
Impact of a Newly Synthesized Molecule (2-chloro-N-(1-(3,4-dimethoxyphenyl) propan-2-yl)-2-phenylacetamide) on the Bioelectrogenesis and the Contractile Activity of Isolated Smooth Muscles
expand article infoVera N. Gledacheva, Iliyana D. Stefanova, Valeri I. Slavchev, Rayna G. Ardasheva, Atanas D. Kristev§, Stoyanka A. Nikolova§, Kremena E. Saracheva|, Darinka S. Dimitrova
‡ Department of Medical Physics and Biophysics, Faculty of Pharmacy, Medical University Plovdiv, Plovdiv, Bulgaria§ Department of Organic Chemistry, Faculty of Chemistry, University of Plovdiv, Plovdiv, Bulgaria| Department of Pharmacology and Drug Toxicology, Faculty of Pharmacy, Medical University Plovdiv, Plovdiv, Bulgaria¶ Department of Pharmacology and Clinical Pharmacology, Faculty of Medicine, Medical University Plovdiv, Plovdiv, Bulgaria
Open Access

Introduction: Examination of the potential possibilities of 2-chloro-N-(1-(3,4-dimethoxyphenyl)propan-2-yl)-2-phenylacetamide (IQP) to affect bioelectrogenesis and the contractile activity of isolated smooth muscles (SM) from stomach.

Aim: Having in mind the structural similarities between the molecules of papaverine and IQP, the aim of the present study was to examine such features of the newly synthesized molecule that may potentially affect the muscle tonus, spontaneous bioelectrical and contractile activities of smooth muscles isolated from the stomach, basing on specific mechanisms of papaverine.

Materials and methods: The synthesis of IQP is based on the initially formed aziridine ring by principles of Gilbert’s reaction. Impact of IQP on the bioelectrogenesis and the contractile activity of isolated smooth muscles from male Wistar rats was measured by the single sucrose-gap method and isometrically recorded.

Results: IQP (1×10-5 – 2.5×10-4 mol/l) causes muscle relaxation, producing changes in two processes that have influence on the mechanical activity of smooth muscles:
1.    Blocked Ca2+ influx through the potential-dependent membrane Ca2+ channels, followed in turn by lowering the Ca2+ intracellular levels. This effect is proved by the changes in the frequency and amplitude of spike-potentials in sucrose-bridge experiments when IQP is applied.
2.    Activation of a cAMP-dependent signal cascade. The relaxing effect of IQP was significantly reduced in the presence of KT5720
(5×10-6 mol/l), an inhibitor of protein kinase A.

Conclusion: We assume that there might be interconnections between these two IQP-dependent processes, because PKA-dependent phosphorylation of the L-type Ca2+ channels in smooth muscles provokes a reaction of inactivation.

biomechanical processes, gastric smooth muscles, isoquinoline skeleton, natural amino acids, new synthesis