Homologation of mexiletine alkyl chain and stereoselective blockade of skeletal muscle sodium channels
| Autor: | De Luca A, Conte Camerino D, Carlo Franchini, Sabata Pierno, Tortorella, Fulvio Loiodice, Andrea Duranti, Giovanni Lentini |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Stereochemistry
medicine.medical_treatment Sodium Muscle Fibers Skeletal chemistry.chemical_element Mexiletine Antiarrhythmic agent Myotonia Mice Drug Discovery medicine Animals Muscle Skeletal Pharmacology Molecular Structure Chemistry Sodium channel Organic Chemistry Electric Conductivity Rana esculenta Skeletal muscle Stereoisomerism Biological activity General Medicine medicine.disease Mice Mutant Strains medicine.anatomical_structure Stereoselectivity Anti-Arrhythmia Agents Sodium Channel Blockers medicine.drug |
| Zdroj: | European Journal of Medicinal Chemistry. 35:147-156 |
| ISSN: | 0223-5234 |
| Popis: | The optical isomers (-)-(S)- and (+)-(R)-3-(2,6-dimethylphenoxy)-2-methyl-1-propanamine (Me2), homologues of the antiarrhythmic and antimyotonic drug mexiletine (Mex), were synthesized and assayed as new potential antimyotonic agents. As observed with Mex, Me2 exhibits an enantioselective behaviour. Tests carried out on sodium currents of single muscle fibres of Rana esculenta demonstrated that (-)-(S)- and (+)-(R)-Me2 were less potent than Mex in producing tonic block, but showed a higher use-dependent block. (-)-(S)-Me2 and (-)-(R)-Mex were also used to study the excitability of muscle fibres of myotonic ADR mice, a phenotype of a recessive form of low GCl myotonia. (-)-(S)-Me2 reduced spontaneous discharges and after discharges better than (-)-(R)-Mex in agreement with the use-dependent block of sodium currents. |
| Databáze: | OpenAIRE |
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