INT23229

Context Info Confidence 0.04 First Reported 1990 Last Reported 2008 Negated 0 Speculated 0 Reported most in Abstract Documents 11 Total Number 11 Disease Relevance 1.87 Pain Relevance 8.56

Anatomy Link Frequency plasma 6 kidney 2 H2-M3 (Mus musculus)

Pain Link Frequency Relevance Heat Morphine 118 100.00 tricyclic antidepressant 4 99.96 addiction 2 98.80 palliative 1 95.68 Opioid 2 90.64 Cancer pain 8 77.60 Bioavailability 1 75.00 Inflammation 1 58.72 Eae 2 33.84 Pain 12 25.00

Disease Link Frequency Relevance Heat Drug Dependence 1 98.80 Vomiting 4 97.84 Cognitive Disorder 1 96.88 Hepatotoxicity 4 90.28 Renal Failure 10 79.36 Delirium 1 79.28 Cancer Pain 8 77.60 INFLAMMATION 1 58.72 Pain 2 5.00 Chronic Renal Failure 2 5.00

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Both morphine-3-glucuronid (M3G) and morphine-6-glucuronid (M6G) are rapidly formed in high concentrations shortly after heroin and morphine consumption.

Positive_regulation (formed) of M3G associated with morphine

1) Confidence 0.04 Published 2008 Journal Pharmacol. Biochem. Behav. Section Abstract Doc Link 18555521 Disease Relevance 0.10 Pain Relevance 0.76

M3G gradually increased after the morphine injection, peaked about 2 days later, then gradually decreased.

Positive_regulation (increased) of M3G associated with morphine

2) Confidence 0.04 Published 2008 Journal J. Vet. Pharmacol. Ther. Section Abstract Doc Link 18307503 Disease Relevance 0 Pain Relevance 1.02

Combined loss of Mrp2 and Mrp3 leads to a substantial accumulation of M3G in the liver, from which it is transported across the sinusoidal membrane at a low rate, resulting in the prolonged presence of M3G in plasma.

Positive_regulation (accumulation) of M3G in plasma

3) Confidence 0.03 Published 2007 Journal Mol. Pharmacol. Section Abstract Doc Link 17485564 Disease Relevance 0 Pain Relevance 0.25

Therefore the accumulation of M6G and M3G is readily explained by kidney failure which is not compensated by CAPD.

Positive_regulation (accumulation) of M3G in kidney

4) Confidence 0.01 Published 1999 Journal Nephrol. Dial. Transplant. Section Body Doc Link 10328468 Disease Relevance 0.12 Pain Relevance 0

RESULTS: While systemic clearance of morphine (1246+/-240 ml/min) was in the range observed in patients with normal kidney function, both M3G and M6G showed substantial accumulation.

Positive_regulation (accumulation) of M3G in kidney

5) Confidence 0.01 Published 1999 Journal Nephrol. Dial. Transplant. Section Body Doc Link 10328468 Disease Relevance 0.16 Pain Relevance 0

Other significant factors were: age greater than 70 years (increased M3G and M6G plasma concentrations), plasma creatinine greater than 150 mumol/L (increased M3G and M6G plasma concentrations), male sex (decreased morphine and M6G plasma concentrations), raised creatinine plus coadministration of tricyclic antidepressants (increased M3G plasma concentrations), ranitidine (increased morphine plasma concentrations), and raised creatinine plus coadministration of ranitidine (increased M6G plasma concentrations).

Positive_regulation (increased) of M3G in plasma associated with tricyclic antidepressant and morphine

6) Confidence 0.01 Published 1990 Journal Clin. Pharmacol. Ther. Section Abstract Doc Link 2401122 Disease Relevance 0.23 Pain Relevance 1.28

Other significant factors were: age greater than 70 years (increased M3G and M6G plasma concentrations), plasma creatinine greater than 150 mumol/L (increased M3G and M6G plasma concentrations), male sex (decreased morphine and M6G plasma concentrations), raised creatinine plus coadministration of tricyclic antidepressants (increased M3G plasma concentrations), ranitidine (increased morphine plasma concentrations), and raised creatinine plus coadministration of ranitidine (increased M6G plasma concentrations).

Positive_regulation (increased) of M3G in plasma associated with tricyclic antidepressant and morphine

7) Confidence 0.01 Published 1990 Journal Clin. Pharmacol. Ther. Section Abstract Doc Link 2401122 Disease Relevance 0.23 Pain Relevance 1.30

Increasing morphine dose was a significant factor for increased plasma concentrations of morphine, M3G, and M6G.

Positive_regulation (increased) of M3G in plasma associated with morphine

8) Confidence 0.01 Published 1990 Journal Clin. Pharmacol. Ther. Section Abstract Doc Link 2401122 Disease Relevance 0.24 Pain Relevance 1.31

Other significant factors were: age greater than 70 years (increased M3G and M6G plasma concentrations), plasma creatinine greater than 150 mumol/L (increased M3G and M6G plasma concentrations), male sex (decreased morphine and M6G plasma concentrations), raised creatinine plus coadministration of tricyclic antidepressants (increased M3G plasma concentrations), ranitidine (increased morphine plasma concentrations), and raised creatinine plus coadministration of ranitidine (increased M6G plasma concentrations).

Positive_regulation (increased) of M3G in plasma associated with tricyclic antidepressant and morphine

9) Confidence 0.01 Published 1990 Journal Clin. Pharmacol. Ther. Section Abstract Doc Link 2401122 Disease Relevance 0.21 Pain Relevance 1.22

In SOP, but not ROP, rabbits, the plasma concentrations of morphine, M3G and M6G were significantly increased compared with those in normal rabbits.

Positive_regulation (increased) of M3G in plasma associated with morphine

10) Confidence 0.00 Published 2003 Journal Int J Pharm Section Abstract Doc Link 14522119 Disease Relevance 0.06 Pain Relevance 0.83

The data indicate that accumulation of M3G and M6G may be a causal or aggravating factor in the nausea and vomiting and cognitive function profile of palliative and terminal care patients with significant renal function impairment.

Positive_regulation (accumulation) of M3G associated with cognitive disorder, vomiting and palliative

11) Confidence 0.00 Published 1997 Journal J Pain Symptom Manage Section Abstract Doc Link 9291702 Disease Relevance 0.53 Pain Relevance 0.58

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