Naloxone potentiates cocaine effect in man.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to R Byck.
Explore the source record for details and available documents.
Eighteen patients undergoing coronary artery surgery were observed to examine whether cocaine in a clinically used dose exerts sympathomimetic effects during general anesthesia. Eleven patients received cocaine hydrochloride as a 10% solution (1.5 mg/kg) applied topically to the nasal mucosa before nasotracheal intubation. Seven patients had a similar procedure without cocaine. Blood pressure, pulse rate, cardiac index, left ventricular stroke work index, total peripheral vascular resistance, and pulmonary vascular resistance were measured. There were no important differences in cardiovascular function between patient groups. The rapid rise in plasma cocaine concentration, reaching 331 ng/mL at 30 minutes and 320 ng/mL at 45 minutes, bore no apparent relationship to any changes in cardiovascular function. We conclude that under conditions of this study, administration of topical cocaine does not exert any clinically significant sympathomimetic effect and appears to be well tolerated in anesthetized patients with coronary artery disease.
Plasma cocaine levels were determined in 7 subjects after intranasal and oral cocaine. Intranasal doses of 0.19, 0.38, 0.75, 1.5, and 2.0 mg/kg were given as a 10% aqueous solution; 0.38 mg/kg was given as crystalline cocaine HCl. Oral cocaine was administered in doses of 2.0 and 3.0 mg/kg. Intranasal cocaine kinetics were described by a 1-compartment open model with 2 consecutive first-order input steps and first-order elimination. Oral cocaine disposition was described by a 1-compartment open model with a lag time followed by a single first-order input phase and first-order elimination. The mean elimination half-life (t 1/2) for cocaine by the intranasal route to 7 subjects was 75 +/- 5 min (mean +/- SE). The mean t 1/2 after oral administration to 4 subjects was 48 +/- 3 min. The relative bioavailability [as determined by the area under the concentration-time curve (AUC)] for the 2.0-mg/kg dose by the intranasal and oral routes was not different. There was a linear increase in AUC with increasing intranasal dose.
Explore the source record for details and available documents.
Endorphins and exogenous opiates inhibit the activity of the noradrenergic nucleus locus coeruleus (LC). This discovery of endorphin transmitters and their interaction with the LC has supported our studies which have suggested that the majority of the signs and symptoms of opiate withdrawal are mimicked by electrical or chemical activation of the LC. We hypothesize that this endorphin-LC connection is critical to opiate action and the withdrawal syndrome. This hypothesis suggests that chronic opiate administration inhibits LC activity and that opiate abstinence after addiction results in a release from inhibition with resultant LC hyperactivity. This hypothesis is supported by recent data suggesting that clonidine as a drug which inhibits the LC and LC-mediated noradrenergic activation, is an efficacious non-opiate treatment for opiate withdrawal. This hypothesis can be tested in man by evaluating drugs which inhibit the LC and LC-mediated behaviors for anti-withdrawal efficacy.
The application of reversed-phase high-performance liquid chromatography to the measurement of benzoylecgonine and cocaine in urine is described. Following a simple extraction and clean-up procedure, chromatography is performed using a column containing an octadecylsilica coated packing, elution with 17% acetonitrile in pH 2.7 phosphate buffer and ultraviolet detection at 200 or 235 nm. The detection limit is ca.0.1 microgram of drug per ml urine, and using the ethyl ester of benzoylecgonine as an internal standard, benzoylecgonine and cocaine are quantified with coefficients of variation of 7.0 and 2.8%, respectively. The procedure has been applied to urines from subjects receiving intranasal cocaine, and compared to the enzyme multiplied immunoassay technique. The chromatography procedure also permits the separation of norcocaine and benzoylnorecgonine.
Cocaine (2.0 milligrams per kilogram) given by the oral route is at least as effective as the same dose given intranasally. Cocaine is not detected in the plasma until 30 minutes after oral administration, but peak plasma concentrations are similar after both routes. The subjective "highs" in man are greater after oral than after intranasal administration.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Using the enzyme immunoassay technique (EMIT), we determined the time course of urinary excretion of benzoylecgonine in 16 surgical patients and three volunteers who received intranasal cocaine. After doses varying from 13 to 130 mg, the test for benzoylecgonine was positive in 1 to 4 h, peaked at about 10 to 12 h, remained positive for 18 to 27 h, and became negative after about 17 h. This information should be considered by drug dependency treatment programs in which the EMIT procedure is used to screen urines for cocaine use.
Actions of morphine include analgesia, sleep, euphoria, and depression of respiration. Transmitter or modulator substances in the brain that have actions similar to morphine may control these functions in man. This hypothesis proposes that enkephalin is a controlling neurotransmitter and its binding to opiate receptors determines mood state as well as influencing respiratory and sleep patterns. Lithium may act through modification of the opiate receptor affinity for an endogenous morphine-like substance. The theory predicts blocking action of naloxone in mania and in most drug-induced euphorias. It implies a new chemical pathophysiological basis for the phenomenology of mental illness.
Cocaine (1.5 milligrams per kilogram) was applied to the nasal mucosa of human subjects. The cocaine persisted in the plasma for 4 to 6 hours and reached peak concentrations of 120 to 474 nanograms per milliliter at 15 to 60 minutes. In that residual cocaine was detectable on the nasal mucosa for 3 hours, continuous absorption secondary to its vasoconstrictive action might explain its persistence in the plasma.
Explore the source record for details and available documents.
Delta(9)-Tetrahydrocannabinol can be applied to tissue in vitro by dissolving it in Pluronic F68 and ethanol. It causes a decrease in size of the compound action potential of the nonmnyelinated fibers of the vagus nerve of the rabbit. This effect appears to be dose-related and chloride-dependent. Effects on other measurable parameters of nerve function seem to be minimal. Although the amounts required seem to be higher than those required to produce hallucinogenic effects in man, this effect is consistent with other work on Delta(9)-tetrahydrocannabinol and may ultimately account for a significant portion of the pharmacological activity of this drug.
Explore the source record for details and available documents.
1. This report is concerned with the question of whether the alpha and delta groups of myelinated A fibres show conduction failure at different temperatures.2. The experiments were done on cat saphenous nerve in vitro. Stimuli were applied to both ends of the nerve and biphasic recordings were taken adjacent to an 11 mm segment of nerve, whose temperature was varied. Before cooling commenced, the stimuli were adjusted so that the action potential which passed through the cold zone and was recorded, collided with the action potential initiated at the opposite end of the nerve.3. Upon cooling the nerve, it was always observed that the delta peak of the action potential which had been previously occluded by collision reappeared at a temperature at which the alpha peak remained occluded.4. The reappearance of the delta peak was reversible upon warming the nerve and was not affected by increasing the interstimulus interval.5. The mean temperature for reappearance of the delta peak was 13.5 degrees C, for reappearance of the alpha peak, 5.3 degrees C.6. In any given nerve, the blocking temperature was replicable and was dependent on the temperature of the cooled segment rather than the gradient between that segment and the remainder of the nerve.7. We conclude that in cat saphenous nerve, the delta group of myelinated A fibres shows conduction failure at a higher temperature than does the alpha group.
Explore the source record for details and available documents.
Explore the source record for details and available documents.