In vivo demonstration of muscarinic receptor binding activity of N-desethyl-oxybutynin, active metabolite of oxybutynin.

The present study was undertaken to characterize in vivo muscarinic receptor binding of N-desethyl-oxybutynin (DEOB), active metabolite of oxybutynin (anticholinergic agent), in the bladder, submaxillary gland, heart and colon of rats, in relation to the plasma concentrations and inhibition of salivation. In the in vitro experiment, DEOB, as well as oxybutynin, inhibited the concentration-dependently specific [3H]N-methylscopolamine (NMS) binding in rat tissues and the affinity of DEOB in the rat bladder, submaxillary gland and colon was significantly (about 2 times) greater than that of oxybutynin. Following i.v. injection of DEOB (2.73-27.3 micromol/kg), there were dose- and time-dependent increases in the apparent dissociation constant (Kd) for specific [3H]NMS binding in the bladder, submaxillary gland, heart and colon of rats, compared with control values, and the effect was similar to that by i.v. injection of oxybutynin (2.54-25.4 micromol/kg). Plasma concentrations of DEOB and oxybutynin in these rats showed dose- and time-dependent increases. The pilocarpine-induced salivary secretion in rats was equipotently reduced by the i.v. injection of DEOB and oxybutynin. In conclusion, it has been shown that intravenously injected DEOB, as well as oxybutynin, binds significantly to muscarinic receptors in rat tissues including the bladder and salivary gland and the receptor binding activity of DEOB is roughly similar to that of oxybutynin.