title: Intra-anal and rectal application of L-erythro methoxamine gel increases anal resting pressure in healthy volunteers.
abstract: BACKGROUND
  This study examined the effect of a single local application of L-erythro methoxamine, an alpha(1)-adrenoceptor agonist, on mean anal resting pressure (MARP) and cardiovascular variables in healthy volunteers.
  
  
  METHODS
  L-Erythro methoxamine gel was administered in a single-blind manner; 0.3-3 per cent gels were applied perianally (n = 12), 1-3 per cent gels intra-anally (n = 16) and 1 per cent gel rectally (n = 8). MARP, systolic blood pressure, diastolic blood pressure and pulse rate were measured before application and for up to 6 h afterwards. Blood samples were taken to estimate plasma drug levels.
  
  
  RESULTS
  Perianal gel produced no increase in MARP. Intra-anal 1 per cent and 3 per cent gel produced a significant rapid rise in MARP for 4 and 5 h respectively after application (P = 0.012 and P = 0.017 respectively). Rectal 1 per cent gel increased MARP for 2 h after application (P = 0.036). Intra-anal gel resulted in an increase in systolic blood pressure (1 per cent gel at 2 h, P = 0.042; 3 per cent gel at 4 h, P = 0.017). One per cent intra-anal and rectal gels caused a decrease in the pulse rate for 2 h after application (P = 0.012 and P = 0.018 respectively). Six subjects complained of nausea and three of headache after gel application.
  
  
  CONCLUSIONS
  Intra-anal and rectal gel produced a sustained rise in MARP with rapid onset in volunteers. This raises the possibility of a therapeutic application for L-erythro methoxamine in patients with passive incontinence and internal anal sphincter dysfunction.
authors.affiliation: Section of Surgery, University Hospital, Queen's Medical Centre, Nottingham NG7 2UH, UK. pashanisar@hotmail.com
authors.forename: P J
authors.initials: PJ
authors.lastname: Nisar
authors.forename: H-J
authors.initials: HJ
authors.lastname: Gruss
authors.forename: D
authors.initials: D
authors.lastname: Bush
authors.forename: N
authors.initials: N
authors.lastname: Barras
authors.forename: A G
authors.initials: AG
authors.lastname: Acheson
authors.forename: J H
authors.initials: JH
authors.lastname: Scholefield
mesh_terms: D000285:Administration, Rectal; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000328:Adult; D001003:Anal Canal / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D005782:Gels; D006801:Humans; D008297:Male; D008365:Manometry; D008729:Methoxamine / Q000008:administration & dosage / Q000494:pharmacology*; D008875:Middle Aged; D011312:Pressure; D011674:Pulse; D016037:Single-Blind Method
chemical_list: D000316:Adrenergic alpha-Agonists; D005782:Gels; D008729:Methoxamine