The Journal of pharmacology and experimental therapeutics
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J. Pharmacol. Exp. Ther. · Sep 1998
Randomized Controlled Trial Comparative Study Clinical TrialComparing the subjective, psychomotor and physiological effects of intravenous pentazocine and morphine in normal volunteers.
The purposes of this study were to characterize the subjective, psychomotor and physiological effects of pentazocine in non-drug-abusing volunteers and to compare and contrast the effects of pentazocine with those of morphine. Sixteen subjects without histories of opiate dependence were injected in an upper extremity vein with 0, 7.5, 15 or 30 mg/70 kg pentazocine or 10 mg/70 kg morphine, using a randomized, double-blind, crossover design. Pentazocine increased scores on the pentobarbital-chlorpromazine-alcohol group and lysergic acid diethylamide scales and decreased scores on the benzedrine group scale of the Addiction Research Center Inventory, increased adjective checklist ratings of "nodding," "sweating" and "turning of stomach" and increased visual analog scale ratings of "difficulty concentrating," "drunk" and "having unpleasant bodily sensations." Pentazocine (30 mg) had a greater propensity to increase ratings associated with dysphoria than did 10 mg of morphine. ⋯ Both pentazocine and morphine induced miosis, but 10 mg of morphine had a greater magnitude of effect than 30 mg of pentazocine. The results of the present study demonstrate that 7.5 to 30 mg of pentazocine had orderly, dose-related effects on subjective, psychomotor and physiological variables. Further, a clinically relevant dose of pentazocine, 30 mg, produced a greater magnitude of dysphoric subjective effects than did 10 mg of morphine, which is consistent with the literature reporting that pentazocine has a greater likelihood of inducing psychotomimesis than do other opioids.
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J. Pharmacol. Exp. Ther. · Sep 1998
Purification of two rat hepatic proteins with A-esterase activity toward chlorpyrifos-oxon and paraoxon.
A-esterases are calcium-dependent hydrolases that can detoxify the active metabolites (oxons) of organophosphorus insecticides such as chlorpyrifos and parathion. A-esterases from rat liver have previously been shown to hydrolyze chlorpyrifos-oxon but not paraoxon at low substrate concentrations. Two A-esterases were extracted by ammonium sulfate fractionation from solubilized rat liver microsomes followed by gel filtration chromatography and preparative scale isoelectric focusing. ⋯ The protein hydrolyzed phenyl acetate, chlorpyrifos-oxon and paraoxon, suggesting that arylesterase and A-esterase activities are attributable to the same liver protein(s). Assays of purified protein and kinetic studies of microsomes suggested that the activity toward high (320 microM) and low (
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J. Pharmacol. Exp. Ther. · Sep 1998
Apparent insensitivity of the hotplate latency test for detection of antinociception following intraperitoneal, intravenous or intracerebroventricular M6G administration to rats.
Although morphine-6-glucuronide (M6G) has been shown to be analgesically active, the relative involvement of spinal and supraspinal structures in mediating M6G's pain-relieving effects following central and systemic administration to rats is unclear. As the tail flick and hotplate latency tests are reported to quantify antinociception mediated primarily by spinal and supraspinal mechanisms respectively, these methods were used to determine the comparative "apparent" levels of antinociception (expressed as percentage maximum possible effect, % MPE) achieved after M6G or morphine administration. Following i.v. or i.p. ⋯ By contrast, antinociception evoked by i.v. morphine (10 micromol) exceeded 50% MPE using both the hotplate and tail flick tests although the "apparent" potency was approximately 2.5 times greater using the tail flick test. After i.c.v. dosing, M6G (0.22-3.3 nmol) was significantly (P < .05) more potent when assessed using the tail flick compared with the hotplate test. Taken together, these data strongly indicate that following central and systemic administration, M6G's antinociceptive effects are mediated primarily by spinal structures whereas both spinal and supraspinal mechanisms contribute to systemic morphine's antinociceptive effects.