The Journal of pharmacology and experimental therapeutics
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J. Pharmacol. Exp. Ther. · Sep 1997
Randomized Controlled Trial Comparative Study Clinical TrialComparing the subjective, psychomotor and physiological effects of intravenous buprenorphine and morphine in healthy volunteers.
The purposes of this study were to characterize the subjective, psychomotor and physiological effects of buprenorphine in nondrug-abusing volunteers and to compare and contrast the effects of equianalgesic doses of buprenorphine and morphine. Sixteen subjects without histories of opiate dependence were injected in an upper extremity vein with 0, 0.075, 0.15 or 0.3 mg/70 kg buprenorphine, or 10 mg/70 kg morphine, using a randomized, double-blind, cross-over design. The 0.3-mg buprenorphine dose and 10-mg morphine dose are considered to be equianalgesic and are doses commonly given for relief of postoperative pain. ⋯ Buprenorphine, but not morphine, decreased respiration rate. The results of our study demonstrate that 0.075 to 0.3 mg buprenorphine had orderly, dose-related effects on subjective, psychomotor and physiological variables. Further, a clinically relevant dose of buprenorphine, 0.3 mg, produced a greater magnitude of subjective and psychomotor-impairing effects than did an equianalgesic dose of morphine.
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J. Pharmacol. Exp. Ther. · Mar 1997
Randomized Controlled Trial Comparative Study Clinical TrialComparing the subjective, psychomotor and physiological effects of intravenous nalbuphine and morphine in healthy volunteers.
The purposes of this study were to characterize the subjective, psychomotor and physiological effects of nalbuphine in healthy non-drug abusing volunteers and to compare and contrast the effects of equianalgesic doses of nalbuphine and morphine. Subjects (12 males, 4 females) without histories of opiate dependence were injected in an upper extremity vein with 0, 2.5, 5.0 or 10 mg/70 kg nalbuphine, or with 10 mg/70 kg morphine, using a randomized, double-blind, crossover design. The 10-mg doses of nalbuphine and morphine are considered equianalgesic and are doses commonly given for relief of postoperative pain. ⋯ The results of the present study demonstrate that 2.5 to 10 mg nalbuphine had orderly, dose-related effects on subjective, psychomotor and physiological variables. The results also indicate that 10 mg of nalbuphine produces a profile of subjective, psychomotor and physiological effects similar to that of an equianalgesic dose of morphine (10 mg). The similarity in profiles between drugs at this dose is consistent with both infrahuman studies, which suggests that nalbuphine is a mu agonist, and studies with nondependent opioid abusers, in which relatively low doses of nalbuphine (such as 10 mg) produce morphine-like effects.
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J. Pharmacol. Exp. Ther. · Sep 1996
Randomized Controlled Trial Clinical TrialPharmacogenetic determination of the effects of codeine and prediction of drug interactions.
To define the differences in codeine pharmacodynamics in extensive (EMs) and poor (PMs) metabolizers of debrisoquin and to determine whether the inhibition of codeine's metabolism by quinidine produces phenotypically dependent pharmacodynamic changes, we studied 16 healthy nonsmoking males, 10 EMs and 6 PMs of debrisoquin. The subjects received in random double-blind fashion 120 mg of codeine plus placebo, 120 mg of codeine plus 100 mg of quinidine and 100 mg of quinidine plus placebo. Blood was obtained over 24 hr and urine was collected for 48 hr. ⋯ Thus, CYP2D6 mediated O-demethylation of codeine to morphine is central to its pharmacodynamic effects. Patients who lack CYP2D6 or whose CYP2D6 is inhibited would not be expected to benefit from codeine. Thus, phenotyping for CYP2D6 and the avoidance of CYP2D6 inhibitors is justified in patients with chronic path before initiating long-term therapy with analgesics whose in vivo activation is dependent on CYP2D6 activity (i.e., codeine, hydrocodone and oxycodone.
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J. Pharmacol. Exp. Ther. · Aug 1994
Randomized Controlled Trial Comparative Study Clinical TrialComparing the subjective, psychomotor and physiological effects of intravenous butorphanol and morphine in healthy volunteers.
The purposes of this study were to characterize the subjective, psychomotor and physiological effects of butorphanol in healthy nondrug-abusing volunteers and to compare and contrast the effects of butorphanol to those of morphine. Into an antecubital vein, the subjects (seven men and five women), who had no history of opiate dependence, were injected with 0, 0.5, 1.0 or 2.0 mg/70 kg of butorphanol or 10 mg/70 kg of morphine; a randomized, double-blind, crossover design was used. The subjective effects of butorphanol included increased scores on the Pentobarbital-Chlorpromazine-Alcohol Group scale and Lysergic Acid Diethylamide scale of the Addiction Research Center inventory; increased visual analog scale ratings of "sedated," "coasting or spaced out" and "difficulty concentrating;" increased adjective checklist ratings of "sweating," "skin itchy" and "sleepy;" and increased "feel drug effect" and drug-liking ratings. ⋯ Also, morphine did not affect a number of ratings that were affected by butorphanol (e.g., "confused," "dreamy," "stimulated," "difficulty concentrating," "floating" or "sweating"). The psychomotor impairing effects of butorphanol, as measured by the Maddox Wing test, an eye-hand coordination test, and the Digit Symbol Substitution Test, were dose related; in contrast, morphine had no effect on psychomotor functioning. Both butorphanol and morphine induced miosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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J. Pharmacol. Exp. Ther. · Mar 1994
Randomized Controlled Trial Clinical TrialAcute effects of pentazocine, naloxone and morphine in opioid-dependent volunteers.
The purpose of this study was to evaluate the agonist and antagonist properties of pentazocine, an opioid mixed agonist-antagonist analgesic, in relation to prototypic opioid agonist and antagonist drugs in opioid-dependent human subjects. Pentazocine (45 and 60 mg), naloxone (0.1 and 0.2 mg), morphine (20, 40 and 60 mg) and saline placebo were administered intramuscularly to six male volunteers maintained on methadone (30 mg/24 hr p.o.), following a double-blind, randomized block order design. Drugs were administered 20 hr after the last dose of methadone. ⋯ Pentazocine precipitated a withdrawal syndrome, but the effects were not dose-dependent, and produced symptoms of confusion and dysphoric changes that were not observed after naloxone administration. Pentazocine was classified as an antagonist by some individuals, and as alcohol or hallucinogen by others. The results of the present study indicate that pentazocine acts in humans as a partial mu agonist with a non-mu component of activity.