Influence of estradiol pretreatment on antimuscarinic action of oxybutynin in rat detrusor muscle.
OBJECTIVE
To investigate the antimuscarinic effect of oxybutynin in the rat detrusor muscle after estrogen pretreatment because, to our knowledge, no study has been done on the interaction of estrogen with antimuscarinic drugs. Estrogen has been shown to affect muscarinic receptors in the detrusor muscle of animals. In addition, oxybutynin has been shown to block muscarinic receptors in the bladder.


METHODS
Estradiol benzoate (150 microg/kg) or saline was given subcutaneously to virgin female Wistar albino rats (n = 6, each group) for 10 consecutive days. On the 11th day, isolated detrusor muscle strips were taken, and acetylcholine (ACh)-induced contractions were evaluated in the absence or presence of oxybutynin (10 and 100 nM).


RESULTS
ACh induced concentration-dependent contractions in the detrusor muscle. In the estradiol-pretreated group, the maximum of the ACh-induced contractions was diminished compared with that in the control group (P < 0.05). Oxybutynin (10 and 100 nM) inhibited ACh-induced contractions competitively (pK(B) 8.85). In the estradiol-pretreated group, the concentration-response curve to ACh was shifted further to the right in the presence of oxybutynin (100 nM).


CONCLUSIONS
We have demonstrated for the first time that oxybutynin further inhibits ACh-induced and muscarinic receptor-mediated contractions in rat detrusor muscle after pretreatment with estrogen.
Yildiz
Oguzhan
O
Department of Medical Pharmacology, Gulhane Military Medical Academy, Etlik, Ankara, Turkey. oyildiz@gata.edu.tr
Ozgok
Yasar
Y
Seyrek
Melik
M
Un
Ismail
I
Kilciler
Mete
M
Tuncer
Meral
M
D000818:Animals; D004347:Drug Interactions; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D008333:Mandelic Acids / Q000494:pharmacology*; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D009130:Muscle, Smooth / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D001743:Urinary Bladder / Q000187:drug effects*
D008333:Mandelic Acids; D018727:Muscarinic Antagonists; D004958:Estradiol; C005419:oxybutynin