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


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, the drugs' ability to displace 3H-QNB from muscarinic receptors was investigated.


RESULTS
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.


CONCLUSIONS
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.
Waldeck
K
K
Department of Clinical Pharmacology, Lund University Hospital, Sweden.
Larsson
B
B
Andersson
K E
KE
D000328:Adult; D000368:Aged; D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008333:Mandelic Acids / Q000378:metabolism / Q000494:pharmacology*; D008875:Middle Aged; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000378:metabolism / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D010306:Parotid Gland / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism; D001743:Urinary Bladder / Q000187:drug effects* / Q000378:metabolism*
D008333:Mandelic Acids; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D001285:Atropine; C032681:desethyloxybutynin; D002217:Carbachol; C005419:oxybutynin