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

The purpose of the study was to evaluate the agonist and antagonist stimulus properties of the mixed opioid agonist antagonists butorphanol and nalbuphine in opioid-dependent subjects. Opioid-dependent volunteers (methadone 30 mg/day, PO) were trained in a three-choice drug discrimination procedure to discriminate between the effects of saline (2 ml), hydromorphone (10 mg/70 kg) and naloxone (0.15 mg/70 kg) administered IM. Subjects earned monetary reinforcement for correctly identifying the training drugs by letter code. Other subjective, behavioral and physiological measures were also collected. Hydromorphone and naloxone increased drug-appropriate responses and other characteristic subjective effects measures. Butorphanol and nalbuphine produced increases in naloxone-appropriate discrimination responding and in those subjective effect measures increased by naloxone. Butorphanol produced greater than 80% naloxone-appropriate responding at 1.05 mg/70 kg; nalbuphine produced 100% naloxone-appropriate responding at 2.1 mg/70 kg. Neither butorphanol nor nalbuphine showed opioid agonist-like effects in these subjects maintained at moderate levels of physical dependence. In opioid-dependent subjects, the stimulus effects of butorphanol and nalbuphine are antagonist-like.
 ...
PMID:Discrimination of butorphanol and nalbuphine in opioid-dependent humans. 170 45

In order to examine the development of tolerance to opioids, eight cynomolgus and two rhesus monkeys were trained to press a lever for food reinforcement and then were catheterized so that drugs could be infused. Three doses of hydromorphone and six different interdose intervals were studied. Hydromorphone infusions initially suppressed lever pressing for food in both species. The rhesus monkeys acquired tolerance to these sedative effects after 14 exposures to the opioid. However, the cynomolgus monkeys failed to acquire tolerance after more than 100 exposures. Naloxone challenge elicited withdrawal symptoms from the rhesus monkeys but not from the cynomolgus monkeys. This differential response to sustained opioid administration in these closely related species suggests that a genetic mechanism may underlie tolerance to and physical dependence on opioids.
 ...
PMID:Cynomolgus monkeys do not develop tolerance to opioids. 618