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Jurna I, Jurna K, Baldauf J, et al. Orales Papaverin reduziert die morphinbedingte Obstipation ohne Abschwächung der Analgesie nach oralem Morphin. [Oral papaverine prevents morphine-induced constipation without interfering with analgesia achieved with oral morphine]. Schmerz. 1996;10(1):27-35doi: 10.1007/s004829600011.
Jurna, I., Jurna, K., Baldauf, J., & Zenz, M. (1996). Orales Papaverin reduziert die morphinbedingte Obstipation ohne Abschwächung der Analgesie nach oralem Morphin. [Oral papaverine prevents morphine-induced constipation without interfering with analgesia achieved with oral morphine]. Schmerz (Berlin, Germany), 10(1), 27-35. https://doi.org/10.1007/s004829600011
Jurna, I, et al. "Orales Papaverin reduziert die morphinbedingte Obstipation ohne Abschwächung der Analgesie nach oralem Morphin." [Oral papaverine prevents morphine-induced constipation without interfering with analgesia achieved with oral morphine]. Schmerz (Berlin, Germany) vol. 10,1 (1996): 27-35. doi: https://doi.org/10.1007/s004829600011
Jurna I, Jurna K, Baldauf J, Zenz M. Orales Papaverin reduziert die morphinbedingte Obstipation ohne Abschwächung der Analgesie nach oralem Morphin. [Oral papaverine prevents morphine-induced constipation without interfering with analgesia achieved with oral morphine]. Schmerz. 1996 Feb 15;10(1):27-35. doi: 10.1007/s004829600011. German. PMID: 12799874.
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Schmerz. 1996 Feb 15;10(1):27-35. doi: 10.1007/s004829600011.

[Oral papaverine prevents morphine-induced constipation without interfering with analgesia achieved with oral morphine].

Schmerz (Berlin, Germany)

[Article in German]
I Jurna, K Jurna, J Baldauf, M Zenz

Affiliations

  1. Institut für Pharmakologie und Toxikologie der Universität des Saarlandes, D-66421 Hamburg.

PMID: 12799874 DOI: 10.1007/s004829600011

Abstract

Long-term administration of morphine for the treatment of chronic pain produces constipation; this requires the use of laxatives, which impair water absorption and upset the electrolyte balance. Morphine-induced constipation is mainly due to inhibition of the propulsive movement of the gastrointestinal tract combined with spastic contraction of smooth circular muscles as a result of drug binding to opioid receptors in the tract. Since papaverine lacks affinity for opioid receptors but relaxes smooth muscle, it seemed possible that oral papaverine might be capable of diminishing constipation without impairing the analgesia achieved with morphine. For this purpose, experiments were carried out on rats: constipation was checked for by measuring the intestinal transit time, and analgesia was assessed by measuring the latency of the tail-flick response to radiant heat or nociceptive activity in single neurons of the thalamus evoked by supramaximal electrical stimulation of afferent C fibres in the sural nerve. Morphine and papaverine were administered by the oral route. Control animals received saline. To measure the intestinal transit time, India ink solution was given orally. Morphine (2.5 and 5 mg/kg orally) prolonged the transit time from approx. 420 min in the controls to more than 600 min, a dose of 2.5 mg/kg producing the maximum effect. Papaverine (0.5, 1, and 2 mg/kg) administered orally together with morphine significantly reduced morphine-induced constipation (Tables 1, 2). Papaverine given alone at a dose of 2 mg/kg caused no change in transit time, while 5 mg/kg significantly increased it (Table 2). The latency of the tail-flick response was increased by oral morphine (2.5 and 5 mg/kg) at 1, 2, and 3 h after administration. Papaverine (0.5, 1 and 2 mg/kg) given in combination with morphine left the antinociceptive effect of morphine unchanged (Figs. 1-3). A study of the nociceptive activity evoked in thalamus neurons of rats under urethane anaesthesia indicated that intestinal absorption of morphine was blocked. Therefore, metoclopramide (0.15 mg/kg) was injected i. v. 10 min before oral administration of morphine or the combination of morphine plus papaverine. Subsequently, morphine produced a dose-dependent depression of evoked nociceptive activity (Fig. 4), the mean effect amounting to 60 % of the control activity and being produced by 2.5 mg/kg (Fig. 5). Since in former experiments on nociceptive activity evoked in thalamus neurones it has been found that the ED(50) of i. v. morphine is 0.05 mg/kg, it is very likely that the presystemic elimination of orally administered morphine is very high and, in addition, that the efficiency of its active metabolite, morphine-6-glucuronide, is rather poor. When morphine 2.5 mg/kg was given together with papaverine 0.5 mg/kg, and morphine 5 mg/kg was administered in combination with papaverine 2 mg/kg, there was no significant reduction in the depressant effect of morphine on nociceptive activity evoked in thalamus neurons (Figs. 6, 7). The results suggest that papaverine given by the oral route may reduce morphine-induced constipation without impairment of the analgesic action of morphine in patients suffering from pain.

References

  1. Eur J Pharmacol. 1981 May 22;71(4):393-400 - PubMed
  2. Am J Gastroenterol. 1980 Sep;74(3):285-91 - PubMed
  3. Med Clin North Am. 1987 Mar;71(2):303-11 - PubMed
  4. Annu Rev Pharmacol Toxicol. 1985;25:249-73 - PubMed
  5. Br J Clin Pharmacol. 1975 Dec;2(6):509-13 - PubMed
  6. Br J Pharmacol Chemother. 1959 Mar;14(1):26-34 - PubMed
  7. Ther Drug Monit. 1991 Jan;13(1):1-23 - PubMed
  8. Brain Res. 1980 Nov 10;201(1):129-41 - PubMed
  9. J Pharmacol Exp Ther. 1975 Nov;195(2):303-10 - PubMed
  10. Neurosci Lett. 1986 Nov 21;71(3):356-60 - PubMed
  11. J Pharmacokinet Biopharm. 1978 Dec;6(6):505-19 - PubMed
  12. Exp Neurol. 1980 Aug;69(2):260-70 - PubMed
  13. Schmerz. 1990 Jun;4(2):65-74 - PubMed
  14. Clin Pharmacol Ther. 1993 Sep;54(3):286-92 - PubMed
  15. Brain Res. 1979 Aug 10;171(3):573-6 - PubMed
  16. Ann Clin Biochem. 1987 Mar;24 ( Pt 2):153-60 - PubMed
  17. Neurosci Lett. 1992 Aug 3;142(1):62-4 - PubMed
  18. Pain. 1988 Mar;32(3):313-26 - PubMed
  19. J Pharm Sci. 1973 Sep;62(9):1416-9 - PubMed
  20. Clin Pharmacol Ther. 1990 Jan;47(1):12-9 - PubMed
  21. Brain Res. 1982 Feb 25;234(2):399-407 - PubMed
  22. Eur J Pharmacol. 1973 Oct;24(1):67-77 - PubMed
  23. Pain. 1983 Apr;15(4):333-44 - PubMed
  24. Cancer Nurs. 1980 Feb;3(1):39-46 - PubMed
  25. Schmerz. 1993 Dec;7(4):314-21 - PubMed
  26. Arzneimittelforschung. 1988 Jul;38(7):877-80 - PubMed
  27. J Pharmacol Exp Ther. 1973 Dec;187(3):575-80 - PubMed
  28. Am J Physiol. 1980 Apr;238(4):G384-9 - PubMed
  29. Life Sci. 1986 Apr 7;38(14):1289-92 - PubMed
  30. J Pharmacol Exp Ther. 1977 Jan;200(1):236-44 - PubMed
  31. Scand J Gastroenterol. 1978;13(3):257-61 - PubMed
  32. Gastroenterology. 1988 Jun;94(6):1351-6 - PubMed

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