L-Erythro-methoxamine is more potent than phenylephrine in effecting contraction of internal anal sphincter in vitro.
BACKGROUND
Topical phenylephrine has been shown to increase resting anal canal pressure in normal and incontinent individuals. However, high concentrations of gel (10-40 per cent) are required that may cause local side-effects. The aim of this study was to determine whether methoxamine, another alpha-1-adrenoceptor agonist, might be a more potent alternative to phenylephrine.


METHODS
Porcine internal anal sphincter (IAS) tissue was cut into strips, suspended in a superfusion organ bath and allowed to equilibrate. Strips were subjected to each drug under test for 20 s, sufficient to obtain stable tone. Phenylephrine, methoxamine (1 : 1 : 1 : 1 ratio of its four isomers) and each of the individual isomers of methoxamine were evaluated in turn.


RESULTS
In vitro, methoxamine racemate and phenylephrine were similarly potent in causing contraction of IAS strips (mean(s.e.m.) dose giving half maximal effect (EC(50)) at 74.7(16.5) versus 58.3(13.4) micro M respectively; P = 0.443). However, one of the methoxamine isomers, L-erythro-methoxamine (EC(50) 17.6(3.7) micro M), was significantly more potent than the other three isomers, methoxamine racemate and phenylephrine (P = 0.002).


CONCLUSIONS
L-Erythro-methoxamine is four times more potent than phenylephrine and is a possible treatment for incontinence. Trials are under way to examine the efficacy of L-erythro-methoxamine in vivo.
Jones
O M
OM
Department of Pharmacology, University of Oxford, Oxford, UK. oliver.jones@pharm.ox.ac.uk
Thompson
J M
JM
Brading
A F
AF
Mortensen
N J McC
NJ
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D001003:Anal Canal / Q000187:drug effects*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D008729:Methoxamine / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology*; D011312:Pressure; D013237:Stereoisomerism; D013552:Swine
D000316:Adrenergic alpha-Agonists; D010656:Phenylephrine; D008729:Methoxamine