Effects of methoctramine on bladder overactivity in a rat model.
OBJECTIVE
To determine the functional effects of methoctramine as an M(2) muscarinic receptor antagonist on isolated detrusor strips in vitro and bladder overactivity in vivo in rats.


METHODS
A total of 114 Sprague-Dawley rats were used in the present study. Isolated rat detrusor strips were contracted by depolarizing the preparations with carbachol. Methoctramine was added to the tissue bath in increasing concentrations, and contraction inhibition was assessed. Isovolumetric contractions were evoked by electrical stimulation using a bipolar electrode. Efficacy against bladder instability was evaluated using the obstructed hypertrophied bladder model in the rat. The acetic acid bladder cystometry model was used to assess the efficacy of methoctramine in neurogenic detrusor overactivity.


RESULTS
Methoctramine inhibited carbachol-induced bladder contractions significantly in isolated rat detrusor strips in a concentration-dependent manner. The amplitude of electrically evoked isovolumetric contractions was decreased significantly after methoctramine exposure. In vivo methoctramine administered intravenously significantly increased the voiding interval and bladder compliance. In addition, a decrease occurred in the number of spontaneous contractions during the filling phase in a model of neurogenic and obstruction-induced detrusor overactivity.


CONCLUSIONS
M(2) antagonists in general may represent a new useful class of drug worth considering in the treatment of bladder overactivity.
Ozturk
Hayrettin
H
Department of Pediatric Surgery, Dicle University Medical School, Diyarbakir, Turkey.
Onen
Abdurrahman
A
Guneli
Ensari
E
Cicek
Ramazan
R
Tas Hekimoglu
Askin
A
D000818:Animals; D018856:Cystitis, Interstitial / Q000188:drug therapy*; D003959:Diamines / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D018727:Muscarinic Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D010276:Parasympatholytics / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000187:drug effects; D001743:Urinary Bladder / Q000187:drug effects* / Q000502:physiology; D001750:Urinary Bladder, Neurogenic / Q000188:drug therapy
D003959:Diamines; D018727:Muscarinic Antagonists; D010276:Parasympatholytics; D011976:Receptors, Muscarinic; C054938:methoctramine