Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0278080 (physical dependence)
 1,658 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A series of morphine-like and nalorphine-like drugs were studied in the nondependent, morphine-dependent and cyclazocine-dependent chronic spinal dog. In the nondependent dog, three profiles of activity were found which could be utilized to distinguish between morphine, WIN 35, 197-2 and cyclazocine. Propiram, a prototypic partial agonist of the morphine type, produced morphine-like effects in nondependent dogs and both precipitated and suppressed abstinence in cyclazocine-dependent dogs as was needed to precipitate abstinence in morphine-dependent dogs. WIN 35, 197-2, a strong agonist in the guinea-pig ileum which has been shown to be resistant to antagonism by naloxone, neither precipitated nor suppressed morphine abstinence but suppressed cyclazocine abstinence. In the nondependent dog, it depressed the flexor reflex but not skin twitch reflex. Cyclazocine altered reflex activity much like WIN 35, 197-2 but produced tachycardia, tachypnea, mydriasis and canine delirum. The morphine and cyclazocine precipitated and withdrawal abstinence syndromes were qualitatively different. Twenty times as much naltrexone was needed to precipitate abstinence in morphine-dependent dogs. Nalorphine both precipitated and suppressed cyclazocine abstinence and appeared to be a partial agonist of the nalorphine-type. Morphine suppressed the cyclazocine abstinence syndrome. Cross-tolerance was not observed in ketocyclazocine-dependent dogs. These data are consistent with the hypothesis that there are strong and partial agonists of the mu and kappa types, and further, that physical dependence on morphine and cyclazocine is mediated through different receptors. WIN 35, 197-2 appears to be a pure strong agonist of the kappa type. Cyclazocine is a mu antagonist and mixed kappa and sigma agonist.
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PMID:The effects of morphine and nalorphine-like drugs in the nondependent, morphine-dependent and cyclazocine-dependent chronic spinal dog. 94 50

The experiments concerned the effects of glucuronate or sulfate conjugation at the 6-position of nalorphine on the analgesic and antagonistic activities and also on the development of tolerance and physical dependence. Nalorphine-3-and 6-sulfate ester were synthesized for the first time. The analgesic effect of nalorphine-6-sulfate and -glucuronide was higher than that of nalorphine when assessed in the acetic acid writhing test. However, these 6-conjugates exhibited less potent agonistic activity in the test with guinea-pig ileum muscle strip and revealed no analgesic effect in the tail pinch test. The antagonistic activity of these 6-conjugates to morphine analgesia was lower on their s.c. injection, but higher on i.c.v. injection than that of nalorphine. The development of tolerance to the analgesia caused by nalorphine was not affected by the 6-modifications. Frequent withdrawal signs were seen in mice treated chronically with anlorphine-6-conjugates by challenging with naloxone while mice treated with nalorphine showed no such signs. This potent enhancing effect of 6-conjugation on the development of physical dependence was suggested to be also the case with morphine. These changes of potency due to conjugation were interpreted as due to the altered interaction with multiple opioid receptors.
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PMID:Potentiation of physical dependence by conjugation at the 6-position of nalorphine. 654 Nov 41