Assessment of agonist and antagonist effects of tramadol in opioid-dependent humans.
The subjective, behavioral, and physiologic effects of racemic tramadol, an analgesic with low abuse liability and dual mu-opioid agonist and monoamine reuptake actions, were evaluated in 2 clinical pharmacology studies in dependent opioid abusers. In the withdrawal precipitation study, participants (N = 8) were maintained on methadone 60 mg/day orally and challenged with intramuscular tramadol, hydromorphone, naloxone, and placebo 20 hr after methadone administration. In the withdrawal suppression study, participants (N = 6) were maintained on hydromorphone given orally 10 mg 4 times daily, and spontaneous opioid withdrawal was produced by withholding doses for 23 hr. During the experimentally induced withdrawal, oral tramadol, hydromorphone, naltrexone, and placebo were given. In both studies a comprehensive panel of participant-rated, observer-rated, and physiologic measures were collected. In both studies, naloxone and naltrexone significantly increased measures of opioid withdrawal, whereas tramadol showed no discernible antagonist effects. In contrast, tramadol's pattern of effects was more similar to that of hydromorphone and suggestive of mild opioid-agonist effects (withdrawal suppression), though not to a statistically significant degree.
Carroll
C Patrick
CP
Behavioral Pharmacology Research Unit, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA. docpat2511@yahoo.com
Walsh
Sharon L
SL
Bigelow
George E
GE
Strain
Eric C
EC
Preston
Kenzie L
KL
D000328:Adult; D000701:Analgesics, Opioid / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D004091:Hydromorphone / Q000494:pharmacology; D008875:Middle Aged; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D009293:Opioid-Related Disorders / Q000188:drug therapy*; D014147:Tramadol / Q000494:pharmacology*
D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D009294:Narcotics; D009270:Naloxone; D014147:Tramadol; D004091:Hydromorphone