l-Erythro-methoxamine is more potent than phenylephrine in effecting contraction of internal anal sphincter in vitro

Abstract

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.

A randomised, controlled, crossover study to investigate the safety and response of 1R,2S‐methoxamine hydrochloride (NRL001) on anal function in healthy volunteers

“…With this in mind, Jones et al [7] compared phenylephrine with a number of methoxamine isomers in vitro and concluded that 1R,2S-methoxamine was four times as potent as phenylephrine, potentially reducing the concentration of drug required to produce a clinically desirable effect. In 2005, Nisar et al compared perianal, intra-anal and intra-rectal application of 1 ml 1R,2S-methoxamine gel in concentrations of 0.3-3% and found a significant rise in MARP with intra-anal and intra-rectal but not perianal application.…”

“…NRL001 (1R,2S-methoxamine hydrochloride) is a stereoisomer of methoxamine hydrochloride that is being developed for the treatment of faecal incontinence as an agent that increases sphincter tone. 1R,2S-methoxamine is four times more potent than phenylephrine [7]. Local intra-anal application of 1R,2S-methoxamine is associated with increases in MARP in healthy volunteers and patients with faecal incontinence [8,9].…”

Intra-anal and rectal application of l-erythro methoxamine gel increases anal resting pressure in healthy volunteers

“…Methoxamine is a highly selective α 1 agonist, with almost no action at α 2 ‐ or β‐adrenoceptors24, and does not gain access to the central nervous system. A study of isolated porcine IAS demonstrated that the synthetic enantiomer L ‐erythro methoxamine has fourfold greater potency in eliciting a contraction than phenylephrine or racemic methoxamine25. The contractile response to L ‐erythro methoxamine is mediated via α 1 ‐adrenoceptors, and it is likely that most of the α 1 ‐agonist activity of racemic methoxamine resides in the enantiomer.…”

A comparison of the contractile properties of smooth muscle from pig urethra and internal anal sphincter

“…Similar results for the IAS have been reported previously. 20 Cumulatively applied carbachol, used to activate muscarinic receptors, contracted urethra with a maximum at 3 Â 10 À4 M but relaxed IAS with a maximum at 10 À3 M. This strongly suggests that the innervation of the two tissues is different.…”