COMPARISON OF OXYBUTYNIN AND ITS ACTIVE METABOLITE, N-DESETHYL-OXYBUTYNIN, IN THE HUMAN DETRUSOR AND PAROTID-GLAND

Purpose: To compare in vitro the antimuscarinic effect of oxybutynin a nd its active metabolite, N-desethyl-oxybutynin, on human detrusor, an d their binding characteristics in detrusor and parotid gland. Materia ls and Methods: 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, th e drugs' ability to displace H-3-QNB from muscarinic receptors was inv estigated. Results: Both oxybutynin and N-desethyl-oxybutynin caused a rightward shift of the concentration-response curve for carbachol wit hout depression of the maximum, indicating a competitive antagonism. T he pA(2) values were 7.8 for oxybutynin and 7.6 for N-desethyl-oxybuty nin. Contractions induced by electrical nerve stimulation were depress ed by 87% by oxybutynin (10 mu M) and by 91% by N-desethyl-oxybutynin (10 mu M). In radioligand receptor binding studies on the detrusor, ox ybutynin and N-desethyl-oxybutynin had uniform displacement curves and the same pK(i) value, 8.2. The affinity for N-desethyl-oxybutynin in the parotid gland was significantly higher, the pK(i) value being 8.7. The corresponding figure for oxybutynin was 8.5. Conclusions: We conc lude that oxybutynin and N-desethyl-oxybutynin have a similar antimusc arinic effect in the human detrusor, and the same binding characterist ics in detrusor and parotid gland, respectively.