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

Abstract

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. 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. 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. 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.