Opioid and nonopioid analgesic drug effects on colon contractions in monkeys

Ferraz, Álvaro Antônio Bandeira; Cowles, Verne E.; Condon, Robert E.; Schulte, William J.

doi:10.1007/bf02285185

Cited by 32 publications

(21 citation statements)

References 14 publications

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“…Although effective as analgesics, opioids increase gastrointestinal tone and intraluminal pressure while simultaneously inhibiting organized propulsive motility. 6,7,18 Opioid analgesics significantly delay recovery from postoperative ileus 1,19 ; their detrimental effects occur with both epidural and parenteral administration. 20 Central and local gastrointestinal opioid receptors contribute to the prolongation of postoperative ileus, but it is likely that gastrointestinal receptors have a more dominant role.…”

Section: Discussionmentioning

confidence: 99%

Selective Postoperative Inhibition of Gastrointestinal Opioid Receptors

et al. 2001

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Section: Discussionmentioning

confidence: 99%

Selective Postoperative Inhibition of Gastrointestinal Opioid Receptors

et al. 2001

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“…In the present study, the effect of YM905 on spastic constipation was tested using the morphineinduced constipation model in ferrets, whose gastrointestinal motility pattern resembles that in humans (24). Since morphine, a m-opioid receptor agonist, causes constipation in vivo by potentiating intermittent tonic contraction and reducing propulsive waves of the colon (25,26), this model can reproduce the bowel behavior similar to that shown in IBS patients with spastic constipation. Our results showed that YM905 reverses morphine-induced constipation with a similar potency to those shown in improving defecation and diarrhea.…”

Section: Discussionmentioning

confidence: 99%

Effects of YM905, a Novel Muscarinic M3-Receptor Antagonist, on Experimental Models of Bowel Dysfunction In Vivo

Kobayashi¹,

Ikeda²,

Suzuki³

et al. 2001

Japanese Journal of Pharmacology

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ABSTRACT-We investigated the effects of YM905 [(+)-(1S,3'R)-quinuclidin-3'-yl 1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate monosuccinate], a new orally active muscarinic M3-receptor antagonist, on bowel dysfunction in vivo using experimental models that reproduce the symptoms present in irritable bowel syndrome (IBS). YM905 potently inhibited restraint stress-induced fecal pellet output in fed rats (ED50: 4.0 mg/ kg) and diarrhea in fasted rats (ED50: 1.7 mg/kg), with similar potencies to the inhibition of bethanechol-, neostigmine-and nicotine-induced fecal pellet output in rats (ED 50: 3.3, 7.9 and 4.5 mg/kg, respectively). YM905 also inhibited 5-hydroxytryptamine (5-HT)-, prostaglandin E2-and castor oil-induced secretory diarrhea in mice (ED50: 5.5, 14 and 6.3 mg/kg, respectively), but showed no significant effect on cholera toxin-induced intestinal secretion in mice. In addition, YM905 (3, 10 mg / kg) reversed morphinedecreased postprandial defecation in ferrets, a model of spastic constipation, whereas remosetron, a 5-HT3-receptor antagonist, was not effective. The mode of YM905 action was similar to that of darifenacin, a selective M3-receptor antagonist, with equivalent potencies. By contrast, propantheline, an antimuscarinic drug that has been used for IBS, was much less potent. These results show that YM905 ameliorates a wide spectrum of bowel dysfunctions through the blockade of M3 receptors, suggesting its therapeutic potential for treating IBS.Keywords: YM905, Muscarinic M3 receptor, Irritable bowel syndrome, Restraint stress, Defecation Irritable bowel syndrome (IBS) is a common functional disorder characterized by symptoms of altered bowel habits, such as frequent stool, diarrhea and/or spastic constipation (1, 2), probably resulting from a dysfunction of the autonomic nerve system (3, 4). In the current therapy, anticholinergic agents have become the standard class of drugs for the control of IBS (5), since they suppress the cholinergic neurotransmission that excitatory regulates gastrointestinal motility by blockage of the muscarinic receptors.Muscarinic acetylcholine receptors have been categorized into five subtypes (M1 -M5) genetically and pharmacologically, although the distribution and biological significance of the M4 and M5 subtypes are not yet well understood (6). Smooth muscle tissues heterogeneously express the M2 and M3 subtypes with a population of approximately 4:1 (7, 8), and M3 receptors are known to play a predominant role in contractile responses in intestinal smooth muscle tissues, including the small intestine (9), ileum (10) and colon (11) under physiological conditions. M 3-receptor antagonists that display fewer effects on M2 receptors would therefore have some therapeutic utility because they scarcely cause M2-associated side effects.YM905 [(+)-(1S,3'R)-quinuclidin-3'-yl 1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate monosuccinate, Fig. 1] is a novel muscarinic M3-receptor antagonist that shows a higher binding affinity for exogeneously expressed human *Corr...

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“…The resulting lack of understanding of the motility pattern is directly related to the type of control which is performed in the colon. The colon suffers direct influences from myogenic factors chiefly represented by the smooth muscle covering, from neural factors involving the central nervous system and the autonomous and enteric nervous systems, and from humoral factors (1)(2)(3)(4)(5)(6)(7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

A spectral analysis of the myoelectric activity of the left colon in patients with schistosomiasis mansoni

Ferraz

2005

Braz J Med Biol Res

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The objective of the present study was to perform a spectral analysis of the electrical activity of the left colon of patients with hepatosplenic schistosomiasis. Thirty patients were studied, divided into 2 groups: group A was composed of 14 patients (9 males and 5 females) with hepatosplenic schistosomiasis and group B was composed of 16 female patients without schistosomiasis mansoni. Three pairs of electrodes were implanted in the left colon at the moment of the surgical treatment. The signals of the electric activity of the colon were captured after postoperative recovery from the ileus and fed into a computer by means of a DATAQ data collection system which identified and captured frequencies between 0.02 and 10 Hz. Data were recorded, stored and analyzed using the WINDAQ 200 software. For electrical analysis, the average voltage of the electrical wave in the three electrodes of all patients, expressed as millivolts (mV), was considered, together with the maximum and minimum values, the root mean square (RMS), the skewness, and the results of the fast Fourier transforms. The average RMS of the schistosomiasis mansoni patients was 284.007 mV. During a long period of contraction, the RMS increased in a statistically significant manner from 127.455 mV during a resting period to 748.959 mV in patients with schistosomiasis mansoni. We conclude that there were no statistically significant differences in RMS values between patients with schistosomiasis mansoni and patients without the disease during the rest period or during a long period of contraction.

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Opioid and nonopioid analgesic drug effects on colon contractions in monkeys

Cited by 32 publications

References 14 publications

Selective Postoperative Inhibition of Gastrointestinal Opioid Receptors

Selective Postoperative Inhibition of Gastrointestinal Opioid Receptors

Effects of YM905, a Novel Muscarinic M3-Receptor Antagonist, on Experimental Models of Bowel Dysfunction In Vivo

A spectral analysis of the myoelectric activity of the left colon in patients with schistosomiasis mansoni

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