piperidines and Hemorrhoids

Despite the prevalence of internal hemorrhoid disease (HD), there are few pharmacologic options. Iferanserin, a selective serotonin receptor antagonist, is being studied for use in the treatment of HD.. This Phase IIb study evaluated the efficacy and tolerability of 10-mg twice-daily iferanserin intra-anal ointment for the cessation of bleeding and other symptoms associated with internal HD.. This randomized, double-blind, placebo-controlled study was conducted at 5 sites in Germany. Outpatients with Goligher grade I, II, and/or III hemorrhoids and bleeding were randomly assigned to receive iferanserin ointment 10 mg or inactive vehicle (placebo) BID for 14 days. During treatment, patients rated the severity of HD symptoms daily on a 10-point scale using a diary form. At enrollment and study end, physicians recorded the frequency and intensity of HD symptoms, adverse events, and results from blood and urine analyses on clinical-report forms.. Of the 121 patients enrolled in the study, 118 were evaluable for tolerability and 111 for efficacy. The mean age of the tolerability population was 52.7 years, 78.9% were male, and all were white. The 2 groups had similar HD symptoms at baseline, but overall, patients in the placebo group had numerically higher grades of HD than did patients in the iferanserin group. Compared with placebo, iferanserin was associated with significantly lower patient-reported severity ratings of daily bleeding and itching, beginning at day 1 for bleeding and at day 2 for itching (P < 0.05), but not with reduced ratings for severity of other HD symptoms, including pain, tenderness, difficulty with defecation, fullness, throbbing, and gas. In the physician assessments, iferanserin was associated with significantly reduced bleeding frequency by day 14 compared with placebo (P < 0.05). Adverse events were mild and infrequent, with no significant differences in prevalences between the 2 treatment groups and no clinically significant changes in laboratory values in any patient.. Compared with placebo, intra-anal iferanserin was associated with significantly reduced patient-reported severity of bleeding and itching and physician-assessed bleeding frequency in these patients presenting with grade I, II, and/or III internal hemorrhoids and bleeding at 5 sites in Germany. ClinicalTrials.gov identifier: 01483833.

Topics: Adolescent; Adult; Aged; Cinnamates; Double-Blind Method; Drug Administration Schedule; Female; Hemorrhoids; Humans; Male; Middle Aged; Piperidines; Prospective Studies; Serotonin Antagonists

Haemorrhoids is associated with high blood flow of the anorectal region. The question of whether pharmacological manipulation of vascular supply can relieve the symptoms of haemorrhoids has been raised. In order to undertake this type of clinical investigation, it is first essential to gain a better understanding of the properties of vascular receptors that may regulate blood flow into anal cushions and haemorrhoids. Due to the limited availability of human anorectal specimens and the good reliability of sheep tissue as an experimental model of human anorectal diseases, we studied the properties of endothelin receptors in sheep rectal artery (SRA) and vein (SRV), the vessels contributing to the blood flow of haemorrhoidal plexus, using isometric tension recordings. We found that endothelin-1 and sarafotoxin 6a were very potent constrictor agents in both SRA and SRV. The selective ET(A) receptor antagonist PD156707 (100 nM) produced a parallel rightward displacement of ET-1-induced contractions in both vessels and abolished sarafotoxin 6a-induced contractions in the SRA. PD156707 (3 μM) practically abolished contractions to ET-1 in the SRA, suggesting that the response is entirely mediated by ET(A) receptors. While, the selective ET(B) receptor antagonist BQ788 (100 nM) caused no significant change in ET-1-induced contractions in both vessels, a minor role for ET(B) receptor subtype to responses to sarafotoxin 6a in the artery was suggested.

Topics: Animals; Antihypertensive Agents; Blood Vessels; Dioxoles; Endothelin A Receptor Antagonists; Endothelin B Receptor Antagonists; Endothelin Receptor Antagonists; Endothelin-1; Hemorrhoids; In Vitro Techniques; Muscle Contraction; Muscle, Smooth, Vascular; Oligopeptides; Piperidines; Potassium Chloride; Receptors, Endothelin; Rectum; Sheep; Vasoconstriction; Vasoconstrictor Agents; Viper Venoms

Topics: Animals; Atropa belladonna; Balsams; Benzimidazoles; Bismuth; Chlorine; Corticosterone; Dibucaine; Ethylamines; Female; Hemorrhoids; Heparin; Hexachlorophene; Hirudin Therapy; Humans; Lidocaine; Menthol; Phenylacetates; Phytotherapy; Piperidines; Plant Extracts; Plants, Medicinal; Plants, Toxic; Prednisolone; Pregnancy; Quinine; Rabbits; Resorcinols; Rutin; Sclerosing Solutions; Terpenes; Zinc