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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

Effect of different doses of morphine on upper gastrointestinal transit in the guinea pig. Values are mean ± SEM. *P < 0.05 and **P < 0.01 in comparison to control.
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f5-jnm-22-529: Effect of different doses of morphine on upper gastrointestinal transit in the guinea pig. Values are mean ± SEM. *P < 0.05 and **P < 0.01 in comparison to control.

Mentions: Three different doses (0.3, 0.5, and 1 mg/kg) of morphine were tested in upper and lower GI transit experiments in order to select the most effective dose for creation of an OIBD model. As shown in Figure 5, the percentage charcoal transit (cm/cm × 100) in the control group was 65.57 ± 10.83, while those in the 0.3, 0.5, and 1 mg/kg morphine treated groups were 48.03 ± 9.87, 38.45 ± 9.20, and 12.72 ± 13.21% respectively. Among the 3 doses tested, dose 1 mg/kg morphine most significantly delayed the charcoal transit in the upper GI tract compared to the control. In the lower GI transit assay the number of fecal pellets expelled in the control group was 15.22 ± 15.78, while those in the 0.3, 0.5, and 1 mg/kg morphine treated groups were 8.00 ± 6.78, 12.16 ± 10.55, and 12.66 ± 10.83 respectively. The comparison of the control group with morphine treated groups clearly showed that the dose 0.3 mg/kg of morphine significantly decreased the cumulative number of fecal pellet output expelled compared to the control (Fig. 6).


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)

Effect of different doses of morphine on upper gastrointestinal transit in the guinea pig. Values are mean ± SEM. *P < 0.05 and **P < 0.01 in comparison to control.
© Copyright Policy
Related In: Results  -  Collection

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

f5-jnm-22-529: Effect of different doses of morphine on upper gastrointestinal transit in the guinea pig. Values are mean ± SEM. *P < 0.05 and **P < 0.01 in comparison to control.
Mentions: Three different doses (0.3, 0.5, and 1 mg/kg) of morphine were tested in upper and lower GI transit experiments in order to select the most effective dose for creation of an OIBD model. As shown in Figure 5, the percentage charcoal transit (cm/cm × 100) in the control group was 65.57 ± 10.83, while those in the 0.3, 0.5, and 1 mg/kg morphine treated groups were 48.03 ± 9.87, 38.45 ± 9.20, and 12.72 ± 13.21% respectively. Among the 3 doses tested, dose 1 mg/kg morphine most significantly delayed the charcoal transit in the upper GI tract compared to the control. In the lower GI transit assay the number of fecal pellets expelled in the control group was 15.22 ± 15.78, while those in the 0.3, 0.5, and 1 mg/kg morphine treated groups were 8.00 ± 6.78, 12.16 ± 10.55, and 12.66 ± 10.83 respectively. The comparison of the control group with morphine treated groups clearly showed that the dose 0.3 mg/kg of morphine significantly decreased the cumulative number of fecal pellet output expelled compared to the control (Fig. 6).

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