Effects of cholinergic agents on anorectal physiology.
BACKGROUND
Despite their potential therapeutic benefit, the effects of cholinergic agents on anal function have been poorly investigated.


OBJECTIVE
To analyse the effects of neostigmine and atropine on anorectal responses to rectal isobaric distension.


METHODS
This was a placebo-controlled, randomized, double-blind crossover study, performed in 12 healthy volunteers who received intravenously, on 3 separate days, neostigmine, atropine or the placebo. During each day of the experiment, seven pressure steps (ranging from 1 to 31 mmHg) in three different protocols of rectal isobaric distension (phasic, stepwise and tonic) were applied using an electronic barostat. Manometric responses of the anal canal, adaptative volumes and perception scores of the rectum were recorded.


RESULTS
During stepwise distension, a significant drug effect was encountered at the anal level. No drug effect was observed on the other investigated parameters (rectal volumes and rectal perception scores) or for the other modes of distension. Compared to placebo, neostigmine significantly decreased pressures at the upper level of the anal canal for both recto anal inhibitory reflex and mean resting pressures. In contrast, atropine significantly increased pressures at the lower part of the anal canal but did not modify upper anal pressures.


CONCLUSIONS
The present study suggests that cholinergic effects result more from an indirect action on intermediate neurotransmitters and rectal myenteric neurons, than from a direct action on anal targets.
Siproudhis
L
L
Gastroenterology Unit, Hôpital Pontchaillou, Rennes, France.
Bellissant
E
E
Juguet
F
F
Allain
H
H
Bretagne
J F
JF
Gosselin
M
M
D000328:Adult; D001003:Anal Canal / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D001285:Atropine / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009197:Myenteric Plexus / Q000187:drug effects / Q000502:physiology; D009388:Neostigmine / Q000494:pharmacology*; D010276:Parasympatholytics / Q000494:pharmacology*; D010465:Perception; D011312:Pressure; D012007:Rectum / Q000187:drug effects* / Q000294:innervation / Q000502:physiology
D010276:Parasympatholytics; D009388:Neostigmine; D001285:Atropine