Evidence map›Paper›PMID 18433425›Full record

Trial reportNeurogastroenterology and motility2008

Relationship of cytochrome P450 pharmacogenetics to the effects of yohimbine on gastrointestinal transit and catecholamines in healthy subjects.

A E Bharucha, T Skaar, C N Andrews, M Camilleri, S Philips, B Seide, D Burton, K Baxter, A R Zinsmeister

Open access · greenAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Neurogastroenterology and motility, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.4field-weighted citation impact, top 35% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 6 citations in OpenAlex.

  1. Trial
  2. Article
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 1 country.

A E BharuchaClinical and Enteric Neuroscience Translational and Epidemiological Research Program (C.E.N.T.E.R.), Mayo Clinic College of Medicine, Rochester, MN 55905, USA. bharucha.adil@mayo.edu
T Skaar
C N Andrews
M Camilleri
S Philips
B Seide
D Burton
K Baxter
A R Zinsmeister
Mayo Clinic · USIndiana University – Purdue University Indianapolis · USMayo Clinic in Florida · US

Funding

ZESTRIL VS. VERAPAMIL IN THE TREATMENT OF HYPERTENSIONM01RR000585 · NCRR · MAYO CLINIC ROCHESTER · PI RIZZA, ROBERT A. · 1985 to 2006
$30.4M
Physiological Characterization and Data Integration CoreP01DK068055 · NIDDK · MAYO CLINIC ROCHESTER · PI FARRUGIA, GIANRICO · 2004 to 2019
$23.8M
NCRR NIH HHS M01 RR000585NCRR NIH HHS M01-RR00585NIDDK NIH HHS P01 DK068055NIDDK NIH HHS R01 DK068055
6 · The paper itself

Abstract

Alpha-2 adrenergic receptors tonically inhibit colonic motility and the alpha(2)-adrenergic antagonist yohimbine, given intravenously, increased colonic tone in humans. However, the effect of yohimbine on colonic transit in humans is unknown. In this study, 30 healthy volunteers were randomized to yohimbine 16.2 mg p.o. t.i.d. or identical placebo for 7 days. We evaluated gastric emptying, small intestinal, and colonic transit by scinitigraphy, bowel habits, haemodynamics and plasma catecholamines. As cytochrome P450 enzymes metabolize yohimbine, P450 genotypes (CYP2D6 and CYP3A4) were determined in 25 of 30 subjects who consented to genetic studies. The relationship between drug metabolizer status predicted by CYP2D6 and CYP3A4 and effects of yohmibine were assessed. Compared to placebo, yohimbine increased (P < or = 0.02) diastolic blood pressure, plasma noradrenaline concentrations and maximum tolerated volume during the satiation test [yohimbine (1241 +/- 88, mean +/- SEM) vs placebo (1015 +/- 87), P = 0.054]. However, yohimbine did not affect gastrointestinal transit. Based on CYP2D6 and CYP3A4 alleles, seven and 18 subjects were, respectively, extensive (EM) and poor (PM) metabolizers of yohimbine. Compared to EM, PM of yohimbine had a greater increase in plasma noradrenaline (P = 0.1 for PM vs EM), lower maximum tolerated volumes (1120 +/- 95 vs 1484 + 131 mL, P = 0.02), and faster colonic transit (i.e. GC(24) was 3.0 +/- 0.4 vs 2.1 +/- 0.5, P = 0.1). These data suggest that CYP2D6 and CYP3A4 genotypes which determine the metabolism of yohimbine may influence its sympathetic and gastrointestinal effects.

Indexed as

PharmacogeneticsAdrenergic alpha-AntagonistsCatecholaminesCytochrome P-450 CYP2D6Cytochrome P-450 CYP3ACytochrome P-450 Enzyme SystemDefecationDouble-Blind MethodFemaleGastrointestinal TransitGenotypeHemodynamicsHumansPlacebosReceptors, Adrenergic, alpha-2SatiationAdrenergic alpha-AntagonistsCatecholaminesCYP3A4 protein, humanCytochrome P-450 CYP2D6Cytochrome P-450 CYP3ACytochrome P-450 Enzyme SystemPlacebosReceptors, Adrenergic, alpha-2Yohimbine

Identifiers

PMID18433425
PMCPMC2574973
OpenAlexW1975405957

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.