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The Effect of DA-9701 in Opioid-induced Bowel Dysfunction of Guinea Pig.

Hussain Z, Rhee KW, Lee YJ, Park H - J Neurogastroenterol Motil (2016)

Bottom Line: Opioid induced bowel dysfunction (OIBD) is associated with decreased gastrointestinal (GI) propulsive activity due to intake of opioid analgesics.In contrast, morphine significantly decreased the amplitude of ileal and distal colon muscle contraction compared to the control.Morphine induced reduction of contractility was significantly ameliorated by addition of DA-9701 in both ileal and distal colon muscles.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.

ABSTRACT

Background/aims: Opioid induced bowel dysfunction (OIBD) is associated with decreased gastrointestinal (GI) propulsive activity due to intake of opioid analgesics. DA-9701, a novel prokinetic agent formulated with Pharbitis Semen and Corydalis Tuber has promising effects on GI motor function. Therefore, we aim to evaluate the prokinetic effects of DA-9701 in an OIBD model of guinea pig.

Methods: The ileal and distal colon muscle contraction in presence of different doses of DA-9701, morphine, and combination (morphine + DA-9701) was measured by tissue bath study. The prokinetic effect of DA-9701 was assessed by charcoal transit and fecal pellet output assay in an OIBD model of guinea pig.

Results: DA-9701 significantly increased the amplitude and area under the curve of ileal muscle contraction, while there was insignificant effect on the distal colon compared to the control. The maximal amplitude of ileal muscle contraction was acquired at a concentration of 10 μg/mL of DA-9701. In contrast, morphine significantly decreased the amplitude of ileal and distal colon muscle contraction compared to the control. Morphine delayed both upper (P < 0.01) and lower (P < 0.05) GI transit, and delayed GI transit was restored by the administration of DA-9701. Morphine induced reduction of contractility was significantly ameliorated by addition of DA-9701 in both ileal and distal colon muscles.

Conclusions: DA-9701 significantly increased the amplitude of contraction of the ileal muscle, however the distal colon muscle contraction was insignificant. Additionally, it restored delayed upper and lower GI transit in an OIBD model of guinea pig, and it might prove to be a useful candidate drug in a clinical trial for OIBD.

No MeSH data available.


Related in: MedlinePlus

Effects of Morphine on contraction of the distal colon muscle. Morphine decreased maximal amplitude and area under the curve (AUC). (A) Percent change of amplitude from control (*P = 0.010). (B) Percent change of AUC from control (*P = 0.010) Values are represented in mean ± SEM.
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f4-jnm-22-529: Effects of Morphine on contraction of the distal colon muscle. Morphine decreased maximal amplitude and area under the curve (AUC). (A) Percent change of amplitude from control (*P = 0.010). (B) Percent change of AUC from control (*P = 0.010) Values are represented in mean ± SEM.

Mentions: In order to generate an OIBD model, we tested the effect of different concentrations of morphine on the amplitude of contraction in the ileal and distal colon muscles. As shown in Figure 3A, out of 6 different doses of morphine analyzed in this study, 1, 3, and 10 μM significantly decreased the amplitude of the contraction in the ileal muscle compared to the control (P = 0.010). The amplitude of ileal muscle contractions were 45.35 ± 33.64%, 45.11 ± 36.86%, 45.57 ± 39.75% in the presence of 1, 3, and 10 μM morphine respectively. In contrast, there was no change in AUC at any dose of the morphine treatment on the ileal muscle (Fig. 3B). In the distal colon muscle, morphine exerts a similar effect on the amplitude as that of the ileal muscle. The doses of 1, 3, and 10 μM had respective amplitude values of 41.23 ± 12.49%, 42.97 ± 11.06%, and 43.58 ± 9.60% respectively, and hence significant decrease from the control (Fig. 4A). Similarly, the AUC of the distal colon also significantly decreased at doses of 1, 3, and 10 μM (Fig. 4B).


The Effect of DA-9701 in Opioid-induced Bowel Dysfunction of Guinea Pig.

Hussain Z, Rhee KW, Lee YJ, Park H - J Neurogastroenterol Motil (2016)

Effects of Morphine on contraction of the distal colon muscle. Morphine decreased maximal amplitude and area under the curve (AUC). (A) Percent change of amplitude from control (*P = 0.010). (B) Percent change of AUC from control (*P = 0.010) Values are represented in mean ± SEM.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4930309&req=5

f4-jnm-22-529: Effects of Morphine on contraction of the distal colon muscle. Morphine decreased maximal amplitude and area under the curve (AUC). (A) Percent change of amplitude from control (*P = 0.010). (B) Percent change of AUC from control (*P = 0.010) Values are represented in mean ± SEM.
Mentions: In order to generate an OIBD model, we tested the effect of different concentrations of morphine on the amplitude of contraction in the ileal and distal colon muscles. As shown in Figure 3A, out of 6 different doses of morphine analyzed in this study, 1, 3, and 10 μM significantly decreased the amplitude of the contraction in the ileal muscle compared to the control (P = 0.010). The amplitude of ileal muscle contractions were 45.35 ± 33.64%, 45.11 ± 36.86%, 45.57 ± 39.75% in the presence of 1, 3, and 10 μM morphine respectively. In contrast, there was no change in AUC at any dose of the morphine treatment on the ileal muscle (Fig. 3B). In the distal colon muscle, morphine exerts a similar effect on the amplitude as that of the ileal muscle. The doses of 1, 3, and 10 μM had respective amplitude values of 41.23 ± 12.49%, 42.97 ± 11.06%, and 43.58 ± 9.60% respectively, and hence significant decrease from the control (Fig. 4A). Similarly, the AUC of the distal colon also significantly decreased at doses of 1, 3, and 10 μM (Fig. 4B).

Bottom Line: Opioid induced bowel dysfunction (OIBD) is associated with decreased gastrointestinal (GI) propulsive activity due to intake of opioid analgesics.In contrast, morphine significantly decreased the amplitude of ileal and distal colon muscle contraction compared to the control.Morphine induced reduction of contractility was significantly ameliorated by addition of DA-9701 in both ileal and distal colon muscles.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.

ABSTRACT

Background/aims: Opioid induced bowel dysfunction (OIBD) is associated with decreased gastrointestinal (GI) propulsive activity due to intake of opioid analgesics. DA-9701, a novel prokinetic agent formulated with Pharbitis Semen and Corydalis Tuber has promising effects on GI motor function. Therefore, we aim to evaluate the prokinetic effects of DA-9701 in an OIBD model of guinea pig.

Methods: The ileal and distal colon muscle contraction in presence of different doses of DA-9701, morphine, and combination (morphine + DA-9701) was measured by tissue bath study. The prokinetic effect of DA-9701 was assessed by charcoal transit and fecal pellet output assay in an OIBD model of guinea pig.

Results: DA-9701 significantly increased the amplitude and area under the curve of ileal muscle contraction, while there was insignificant effect on the distal colon compared to the control. The maximal amplitude of ileal muscle contraction was acquired at a concentration of 10 μg/mL of DA-9701. In contrast, morphine significantly decreased the amplitude of ileal and distal colon muscle contraction compared to the control. Morphine delayed both upper (P < 0.01) and lower (P < 0.05) GI transit, and delayed GI transit was restored by the administration of DA-9701. Morphine induced reduction of contractility was significantly ameliorated by addition of DA-9701 in both ileal and distal colon muscles.

Conclusions: DA-9701 significantly increased the amplitude of contraction of the ileal muscle, however the distal colon muscle contraction was insignificant. Additionally, it restored delayed upper and lower GI transit in an OIBD model of guinea pig, and it might prove to be a useful candidate drug in a clinical trial for OIBD.

No MeSH data available.


Related in: MedlinePlus