Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085631 (agitation)
 12,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Morphine sulfate in doses of 90 to 150 micrograms/3 microliters evoke a prominent behavioral syndrome characterized by 1) periodic bouts of spontaneous agitation during which the rat scratches and bites at the skin of the caudal dermatomes and 2) vigorous agitation, vocalization and coordinated efforts to bite and escape evoked by a light tactile stimulus applied to the flank, suggestive of a pain state (allodynia). The phenomenon is not reversed by naltrexone or is it subject to tolerance. The ordering of activity of an opioid alkaloid related agent in producing this touch-evoked agitation is: noroxymorphone-3-glucuronide, morphine-3-glucuronide, morphine-3-ethereal sulfate, dihydromorphine, noroxymorphone dihydrate, hydromorphone, dihydrocodeine tartrate, morphine sulfate, dihydroisomorphine, morphine-HCl, 6-acetylmorphine, N-normorphine-HCl and (+)-morphine. The following agents were essentially without effect at the highest doses examined: 3,6-diacetylmorphine, N-normeperidine-HCl, nalorphine-HCl, alfentanil, sufentanil, naloxone, naltrexone, methadone, dextrorphan tartrate, meperidine-HCl, oxycodone, levorphanol, oxymorphone, codeine phosphate, thebaine, nalbuphine and naltrexone-3-glucuronide. The observations that the sulfated and conjugated metabolites are 10 to 50 times more potent than their unmetabolized precursor suggest the possibility that, in high concentrations certain phenanthrene opioid alkaloids with a free 3-OH position, an ether bridge and no N-methyl extension will be subject to conjugation and this metabolite will alter the processing of otherwise innocuous tactile stimuli. The fact that the phenomenon appeared at least partially stereospecific may reflect upon the fact that other laboratories have shown that glucuronyl transferase may preferentially convert (-)-morphine to the 3-glucuronide and (+)-morphine to the 6-glucuronide which may be less active.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacology of the allodynia in rats evoked by high dose intrathecal morphine. 334 33

Morphine sulfate is often used to treat severe pain. Pharmacists have been requested to compound morphine sulfate sustained-release capsules in dosages that are not available commercially. However, there has been considerable controversy about the advisability of that practice. This study determined the release of six formulations of 300 mg morphine sulfate sustained-release capsules by means of a United States Pharmacopeia (USP) type III dissolution apparatus. The formulation suggested by a reputable compounding consulting company released almost half the morphine in the first hour of a time-release test and did not adequately sustain the release of the remainder. With increases in the level of hydroxypropyl methylcellulose (Methocel), the release was prolonged and the amount of drug released during the first hour was reduced. One formulation of encapsulated compressed pellets showed that the release could be sustained significantly beyond that of the original formulation. In addition, the increased agitation that occurs in the gastointestinal tract when the medication is taken after a meal reduced the period of sustained release and slightly increased the amount of morphine released during the first hour after administration. In conclusion, the original formula of morphine sulfate sustained-release capsules (Formula A) is probably not adequate for most applications. The formulations with a greater percentage of Methocel are preferred. In addition, the pelleted formulation was superior; however, it may not be feasible to use this labor-intensive approach to compound capsules.
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PMID:Release of morphine sulfate from compounded slow-release capsules: the effect of formulation on release. 2398 79