Patent Evaluation: Tetrahydroprotoberberine quaternary compounds as antiarrythmic agents

Summary

Novelty: Tetrahydroprotoberberine quaternary compounds are claimed which suppress arrhythmia and ventricular fibrillations. The compounds protect against myocardial ischaemia and can be conveniently administered orally.

Biology: A number of assays were performed to determine protection against arrhythmia, ventricular fibrillation and myocardial ischaemic injury. One of the compounds had an ED₅₀ of 0.22 (iv) against arrhythmias and 0.016 mg/kg against ventricular fibrillation. After po administration ED₅₀ values were 16.5 and 20 mg/kg, respectively.

Chemistry: The synthesis of five compounds is described. They are prepared in two steps starting from protoberberine and involve reduction with potassium borohydride followed by alkyfation with an alkyl halide.