Analgesic profile of rimazolium as compared to different classes of pain killers

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Abstract

1,6-Dimethyl-3-carbethoxy-4-oxo-6,7,8,9-tetrahydro-homopyrimidazol (rimazolium, MZ-144) proved to be effective in all the analgesic assays used (independently of the nociceptive stimulus applied) (hot plate, tail flick, writhing tests, Randall-Selitto test, tail clip, surgical pain) differing in this respect from the nonsteroidal antiinflammatory analgetics. The analgesic, antiinflammatory and gastrointestinal effects of rimazolium, morphine and prostaglandin synthesis inhibitors were compared. The prostaglandin (PG) mediated pain (acetylcholine-, adenosine triphosphate- and acetic acid-induced writhing) was inhibited by all the three types of compounds, however, pain reduction where PGs are not involved (MgSO4-writhing) was inhibited only by rimazolium and morphine but not, or only slightly, by PG synthesis inhibitors. While the analgesic effect of rimazolium alone was not reversed by naloxone, the full analgesia evoked by the ineffective doses of morphine and rimazolium combinations was completely naloxone reversible (pA2 = 8.6). In addition, rimazolium produced weak analgesia by intrathecal administration, and its concomitant s.c. administration enhanced the analgesic effect of intrathecally administered morphine. Furthermore, chronic treatment with rimazolium failed to influence its analgesic activity and no tolerance developed and no naloxone precipitated withdrawal syndrome could be seen. In addition, rimazolium did not substitute for morphine in morphine dependent rats, after morphine withdrawal, thus indicating that rimazolium lacks the capacity of producing opiate-like physiological dependence. Also rimazolium fails to show any indication of narcotic-like abuse liability by any of clinical assessments. Rimazolium, morphine and indometacin inhibited the carrageenin-induced edema formation. Gastrointestinal lesions produced by indometacin were depressed by rimazolium and enhanced by morphine. These results also suggest different mechanisms of antiinflammatory and analgesic action of rimazolium, morphine and PG synthesis inhibitors.

Original languageEnglish
Pages (from-to)552-557
Number of pages6
JournalArzneimittel-Forschung
Volume38
Issue number4
Publication statusPublished - 1988

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Analgesics
Morphine
Pain
Prostaglandin Antagonists
Prostaglandins
Naloxone
Anti-Inflammatory Agents
probon
Indomethacin
Analgesia
Tail
Opiate Alkaloids
Opioid-Related Disorders
Carrageenan
Narcotics
Surgical Instruments
Acetic Acid
Acetylcholine
Rats
Assays

ASJC Scopus subject areas

  • Chemistry(all)
  • Organic Chemistry
  • Drug Discovery
  • Pharmacology

Cite this

Analgesic profile of rimazolium as compared to different classes of pain killers. / Fürst, S.; Gyires, K.; Knoll, J.

In: Arzneimittel-Forschung, Vol. 38, No. 4, 1988, p. 552-557.

Research output: Contribution to journalArticle

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abstract = "1,6-Dimethyl-3-carbethoxy-4-oxo-6,7,8,9-tetrahydro-homopyrimidazol (rimazolium, MZ-144) proved to be effective in all the analgesic assays used (independently of the nociceptive stimulus applied) (hot plate, tail flick, writhing tests, Randall-Selitto test, tail clip, surgical pain) differing in this respect from the nonsteroidal antiinflammatory analgetics. The analgesic, antiinflammatory and gastrointestinal effects of rimazolium, morphine and prostaglandin synthesis inhibitors were compared. The prostaglandin (PG) mediated pain (acetylcholine-, adenosine triphosphate- and acetic acid-induced writhing) was inhibited by all the three types of compounds, however, pain reduction where PGs are not involved (MgSO4-writhing) was inhibited only by rimazolium and morphine but not, or only slightly, by PG synthesis inhibitors. While the analgesic effect of rimazolium alone was not reversed by naloxone, the full analgesia evoked by the ineffective doses of morphine and rimazolium combinations was completely naloxone reversible (pA2 = 8.6). In addition, rimazolium produced weak analgesia by intrathecal administration, and its concomitant s.c. administration enhanced the analgesic effect of intrathecally administered morphine. Furthermore, chronic treatment with rimazolium failed to influence its analgesic activity and no tolerance developed and no naloxone precipitated withdrawal syndrome could be seen. In addition, rimazolium did not substitute for morphine in morphine dependent rats, after morphine withdrawal, thus indicating that rimazolium lacks the capacity of producing opiate-like physiological dependence. Also rimazolium fails to show any indication of narcotic-like abuse liability by any of clinical assessments. Rimazolium, morphine and indometacin inhibited the carrageenin-induced edema formation. Gastrointestinal lesions produced by indometacin were depressed by rimazolium and enhanced by morphine. These results also suggest different mechanisms of antiinflammatory and analgesic action of rimazolium, morphine and PG synthesis inhibitors.",
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