title: The pharmacology of the internal anal sphincter and new treatments of ano-rectal disorders.
abstract: Surgical options for faecal incontinence in the presence of intact sphincters are limited. Furthermore, in patients with fissures, lateral sphincterotomy reduces anal sphincter hypertonia but there has been concern about complications. A greater understanding of the basic pharmacology of the internal anal sphincter has led to the development of novel treatments for both these disorders. A Medline review was undertaken for internal anal sphincter pharmacology, anal fissures and faecal incontinence. This review is based on these articles and those found by further cross-referencing. Nitric oxide released from non-adrenergic non-cholinergic nerves is the main inhibitory agent in the internal anal sphincter. Relaxations are also mediated through beta-adrenoceptors and muscarinic receptors. Stimulation of alpha-receptors results in contraction. Calcium and its entry through L-type calcium channels is important for the maintenance of tone. Nitric oxide donors produce reductions in resting anal tone and heal fissures but are associated with side-effects. Muscarinic agents and calcium channel antagonists show promise as low side-effect alternatives. Botulinum toxin appears more efficacious than other agents in healing fissures. To date, alpha-receptor agonists have been disappointing at improving incontinence. Further understanding of the pharmacology of the internal anal sphincter may permit the development of new agents to selectively target the tissue with greater efficacy and fewer side-effects.
authors: University Department of Pharmacology, John Radcliffe Hospital, Oxford, UK. resnaith@hotmail.com
authors: T A
authors: TA
authors: Cook
authors: A F
authors: AF
authors: Brading
authors: N J
authors: NJ
authors: Mortensen
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D001003:Anal Canal / Q000187:drug effects* / Q000294:innervation / Q000502:physiology*; D001905:Botulinum Toxins / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000502:physiology; D005242:Fecal Incontinence / Q000188:drug therapy* / Q000601:surgery; D006801:Humans; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D009126:Muscle Relaxation; D009569:Nitric Oxide / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000502:physiology*
chemical_list: D000316:Adrenergic alpha-Agonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D009569:Nitric Oxide; D001905:Botulinum Toxins