The Journal of pharmacology and experimental therapeutics
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J. Pharmacol. Exp. Ther. · May 1977
Conduction-blocking concentrations of anesthetics increase with nerve axon diameter: studies with alcohol, lidocaine and tetrodotoxin on single myelinated fibers.
The equilibrium blocking concentrations of benzyl alcohol, lidocaine and tetrodotoxin just sufficient to block nerve impulse conduction were determined on myelinated single fibers of the bullfrog. For all three anesthetics it was found that the fastest conducting fibers (45 m/sec; about 18 micron diameter) required about 4 times higher blocking concentrations than the slowest fibers (8 m/sec; about 3 micron diameter). ⋯ J. Physiol. 10: 267-274, 1960), it is concluded that smaller myelinated fibers are more sensitive to anesthetic blockade.
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J. Pharmacol. Exp. Ther. · Apr 1977
Comparative StudyEffects of cocaine and d-amphetamine on behavior maintained under various schedules of food presentation in squirrel monkeys.
Dose-response functions were determined for the effects of cocaine and d-amphetamine on lever-pressing responses maintained under three schedules of food presentation: 1) a simple fixed-ratio schedule, 2) a multiple fixed-ratio, fixed-interval schedule and 3) a second-order fixed-interval schedule with fixed-ratio components. These schedules generated a variety of rates and patterns of responding. The effects of the drugs on response rate depended on the control rates of responding. ⋯ Under the second-order schedule and the multiple schedule, local response rates during successive segments of the fixed-intervals were differentially affected by the drugs. Cocaine and d-amphetamine markedly increased low response rates that occurred during initial segments of the fixed intervals, but either had little effect on or decreased higher responses rates that occurred during later segments of the fixed intervals. Cocaine and d-amphetamine had similar qualitative and quantitative effects on responding, but d-amphetamine was longer lasting than cocaine.
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J. Pharmacol. Exp. Ther. · Nov 1976
Comparative StudyInteractions between narcotic analgesics and benzodiazepine derivatives on behavior in the mouse.
Interactions between the benzodiazepine derivatives, diazepam and oxazepam, and the narcotic analgesics, morphine and methadone, were evaluated on locomotor activity and in the tail-flick and hot-plate tests for analgesia in the mouse. The dose-related stimulation of locomotor activity by morphine was reduced by diazepam and oxazepam at doses which alone had no effect on locomotor activity. However, only oxazepam reduced the dose-related stimulation of locomotor activity by methadone. ⋯ In contrast to the results on locomotor activity, neither of these benzodiazepines significantly modified the dose-response curves of morphine or methadone in either test for analgesia. The mechanisms involved in the observed interactions on locomotor activity may be related to the influences of benzodiazepines and narcotic analgesics on motor efferent pathways summating in such a manner as to interfere with the ability of the mice to locomote. The present results demonstrate that prominent interactions occur between members of the benzodiazepine and narcotic analgesic classes; these interactions are dependent upon both the specific combination of drugs administered and upon the test procedure.
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J. Pharmacol. Exp. Ther. · Jul 1976
Effects of d-amphetamine, pentobarbital, chlorpromazine and promazine on electric shock postponement responding by the pigeon.
The effects of d-amphetamine, pentobarbital, chlorpromazine and promazine on responding under schedules of electric shock postponement were studied in pigeons. Responding was maintained by three different response-shock intervals (10, 20 and 60 seconds). Low doses (0.3-3 mg/kg) of d-amphetamine increased response rates without decreasing shock rates under all three response-shock intervals. ⋯ Chlorpromazine (3-100 mg/kg) did not affect the average rate of responding under all response-shock intervals and only slightly increased shock rates under the 20- and 60-second response-shock intervals. Promazine (3-30 mg/kg) increased the rates of responding and decreased shock rates under all three response-shock intervals. Analysis of the temporal patterns of responding within the response-shock interval showed that d-amphetamine tended to induce the animals to respond earlier than they normally would in the response-shock interval while otherwise maintaining the temporal pattern of responding, pentobarbital decreased the probability of responses late in the response-shock interval, and chlorpromazine and promazine increased the probability of responses in the middle of the response-shock interval, producing a lessening of the temporal patterning of responding within the response-shock interval.
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J. Pharmacol. Exp. Ther. · Apr 1976
Methadone during pregnancy in the rat: dose level effects on maternal and perinatal mortality and growth in the offspring.
Four groups of pregnant rats were administered methadone hydrochloride orally on days 8 through 22 of gestation. Each group initially received 5 mg/kg for 4 days. One group was maintained at this level and the remaining groups were increased to maintenance doses of 10, 15 or 20 mg/kg increments at 4-day intervals. ⋯ Body weights of offspring of mothers in the 20 mg/kg group remained well above average through weaning. In a second experiment, blood levels of methadone were determined for both mothers and litters in the 5, 10 and 15 mg/kg groups, sacrificed 24 hours before expected parturition. Blood levels were dose-related and corresponded to those found in human subjects receiving daily maintenance doses of approximately 30, 60 and 100 mg, respectively.