Comparison of oxybutynin and its active metabolite, N-desethyl-oxybutynin, in the human detrusor and parotid gland.

Abstract

To compare in vitro the antimuscarinic effect of oxybutynin and its active metabolite, N-desethyl-oxybutynin, on human detrusor, and their binding characteristics in detrusor and parotid gland. Antimuscarinic effect in the detrusor was assessed as the ability of the drugs to inhibit carbachol-induced contractions and contractions induced by electrical nerve stimulation. In addition, the drugs' ability to displace 3H-QNB from muscarinic receptors was investigated. Both oxybutynin and N-desethyl-oxybutynin caused a rightward shift of the concentration-response curve for carbachol without depression of the maximum, indicating a competitive antagonism. The pA2 values were 7.8 for oxybutynin and 7.6 for N-desethyl-oxybutynin. Contractions induced by electrical nerve stimulation were depressed by 87% by oxybutynin (10 microM) and by 91% by N-desethyl-oxybutynin (10 microM). In radioligand receptor binding studies on the detrusor, oxybutynin and N-desethyl-oxybutynin had uniform displacement curves and the same pKi value, 8.2. The affinity for N-desethyl-oxybutynin in the parotid gland was significantly higher, the pKi value being 8.7. The corresponding figure for oxybutynin was 8.5. We conclude that oxybutynin and N-desethyl-oxybutynin have a similar antimuscarinic effect in the human detrusor, and the same binding characteristics in detrusor and parotid gland, respectively.