Pseudobase formation in 2-methylpapaverinium cations and their biotransformation by enzymes of rat liver homogenates in vitro

Abstract

2-Methylpapaverinium iodide (I), 2'-hydroxymethyl-2-methylpapaverinium iodide (IX), and 2-methyl-3,4-dihydropapaverinium iodide (X. CH3I) form pseudobase by addition of hydroxide ions to the C(1)=N(+) bond. 2'-Hydroxymethyl-2-methyl-3,4-dihydropapaverinium iodide (XV) and 2'-hydroxymethyl-2-methyl-9-oxo-3,4-dihydropapaverinium iodide (XVI) react with hydroxide ions in aqueous medium under formation of cyclic pseudobases XVII and XVIII. The equilibrium constants (KR+) of pseudobase formation have been measured in aqueous ethanol (1 : 1 w/w, 25°C, ionic strength 0.1). The quaternary papaverinium derivatives are metabolized to isoquinilones and carbonyl compounds by means of rat liver enzymes. The role of pseudobases in these biotransformations has been discussed and biogenetic conclusions have been drawn.