Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085632 (apathy)
 4,089 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of graded doses of nalorphine and morphine were studied in nondependent chronic spinal dogs. Morphine and low doses of nalorphine produced behavioral changes characterized by indifference, whereas the largest dose of nalorphine produced canine delirium indistinguishable from that produced by SKF-10, 047 or cyclazocine. Nalorphine depressed the flexor reflex; however, a plateau was observed. The data suggest that nalorphine is a partial agonist of the kappa type and a sigma agonist in addition to being a competitive antagonist at the mu receptor, and further, that the dysphoric and hallucinogenic effects of nalorphine-like drugs are due to their sigma activity.
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PMID:Sigma effects of nalorphine in the chronic spinal dog. 18 82

Three different syndromes produced by congeners of morphine have been identified in the nondependent chronic spinal dog. These syndromes have been attributed to interaction of agonists with three distinguishable receptors (mu, kappa and sigma). Morphine is the prototype agonist for the mu receptor, ketocyclazocine for the kappa receptor and SKF-10,047 for the sigma receptor. The morphine syndrome (mu) in the dog is characterized by miosis, bradycardia, hypothermia, a general depression of the nociceptive responses and indifference to environmental stimuli. Ketocyclazocine (kappa) constricts pupils, depresses the flexor reflex and produces sedation but does not markedly alter pulse rate or the skin twitch reflex. SKF-10,047 (sigma), in contrast to morphine and ketocyclazocine, causes mydriasis, tachypnea, tachycardia and mania. The effects of these three drugs can be antagonized by the pure antagonist naltrexone, indicating that they are agonists. Further, chronic administration of morphine, ketocyclazocine and SKF-10,047 induces tolerance to their agonistic effects. Morphine suppresses abstinence in morphine-dependent dogs while ketocyclazocine does not. Ketocyclazocine at best precipitated only a liminal abstinence syndrome in the morphine-dependent dog, indicating that it had little affinity for the morphine receptor. Ketocyclazocine thus appears to be a selective agonist at the kappa receptor. Further, it has been shown that buprenorphine is a partial agonist of the mu type which both suppressed and precipitated abstinence in the morphine-dependent dog while morphine and propoxyphene are stronger agonists. Apomorphine and SKF-10,047 produce similar pharmacologic effects suggesting that sigma activity may involve a dopaminergic mechanism.
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PMID:The effects of morphine- and nalorphine- like drugs in the nondependent and morphine-dependent chronic spinal dog. 94 47