Robert Byck

Monosodium L-glutamate: its pharmacology and role in the Chinese restaurant syndrome.

Monosodium L-glutamate is the cause of the Chinese restaurant syndrome and can precipitate headaches. In appropriate doses it causes burning sensations, facial pressure, and chest pain. These are pharmacological effects obeying a dose-effect relationship. There is considerable variation in oral threshold does among individuals.

Intranasal and oral cocaine kinetics

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 (t½) for cocaine by the intranasal route to 7 subjects was 75 ± 5 min (mean±SE). The mean t½ 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.

Plasma cocaine concentrations during cocaine paste smoking

Cigarettes containing cocaine paste were administered to experiences volunteer smokers in Peru, and plasma concentrations of cocaine were measured. Cocaine concentrations as high as 462 ng/ml were obtained after only three minutes of smoking cocaine paste. Subjects titrated their rate of consumption so as to achieve remarkably constant plasma concentrations during the smoking period. Areas under curve (AUC), adjusted for dose, were approximately 70% that obtained with oral or intranasal administration of cocaine to different subjects in previous experiments.

PEPTIDE TRANSMITTERS: A UNIFYING HYPOTHESIS FOR EUPHORIA, RESPIRATION, SLEEP, AND THE ACTION OF LITHIUM

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.

Measurement of benzoylecgonine and cocaine in urine, separation of various cocaine metabolites using reversed-phase high-performance liquid chromatography

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.

Intravenous cocaine challenges during naltrexone maintenance: A preliminary study

In 1976 Byck hypothesized that opioid antagonists would block the euphoric effect of cocaine, and recent clinical observations have suggested lower rates of cocaine abuse by people receiving naltrexone (NTX) than by those receiving methadone (Kosten et al 1989). Although early workers found that both rodents and primates maintained on antagonists showed no attenuation of cocaine self-administration (Killian et al 1978; Carroll et al 1986), more recent studies have found attenuation with NTX administration (Mello et al 1990; DeVry et al 1989; Ramsey and van Ree 1991). Furthermom, Bain and Kornetsky (1987), using rewarding brain stimulation in rodents, showed that the antagonist naloxone can reverse cocaines potentiation of this stimulation. An early human study using cocaine administration found a potentiation rather than a reduction of cocaine effect after acute high-dose naloxcne (20 mg i.e.; Byck et al 1982), but this situation is clearly different from maintenance blocking with lower doses of NTX. We therefore undertook the current cocaine challenge study during chronic NTX.

Intranasal Cocaine: Dose Relationships of Psychological Effects and Plasma Levels:

We compared the psychological effects of three doses of intranasal cocaine hydrochloride (.2, .75, and 1.5 mg/kg) with cocaine plasma concentrations in four volunteers. Intranasal lidocaine hydrochloride (.2 mg/kg) was used as a topically active placebo. Peak “high” ratings were related to both dose and peak plasma concentrations. At a given plasma concentration, “high” ratings were greater when plasma levels were increasing than when they were decreasing. This indicates that acute tolerance by tachyphylaxis occurred after single doses. The cocaine “high” was a pleasant feeling but was without distinctive sensations. The dramatic effects of intranasal cocaine on the street may be related to larger or repeated doses as well as the setting.

Cocaine and lidocaine have similar psychological effects after intranasal application.

Abstract Drug experienced subjects were administered three matched doses of intranasal cocaine and lidocaine. For each dose psychological ratings were similar for both drugs. The subjects were unable to discriminate between the drugs.

Cocaine: 1884–1974

Cocaine, because of its unique properties as a local anesthetic, is still widely used in medicine some one hundred years after its introduction to Europe as a panacea. Karl Koller’s discovery of the local anesthetic action of cocaine defined its legitimate medical usage. Today, cocaine is a drug of abuse that has dramatically increased in popularity. It is reported to produce an intense euphoria 3–5 minutes after intranasal application and thereby has gained the reputation of being the “champagne of drugs.”

Decreased digital flow persists after the abatement of cocaine-induced hemodynamic stimulation.

This study determined whether the development of delayed ischemic sequelae due to cocaine use-after the return of arterial blood pressure (BP) and heart rate to near-baseline values-may be attributable to regional vasoconstriction which persists beyond the acute systemic hemodynamic response. Five cocaine-using volunteers received intravenous infusions of saline placebo and cocaine 0.50 mg/kg several days apart in a double-blinded cross-over design. The intensity and duration of the cocaine-induced decrease in peripheral blood flow (as documented by laser Doppler flowmetry of the finger) were compared to the increases in BP (obtained with a Dinamap [R]) and heart rate using paired t-test and repeated-measures analysis of variance. A significant increase in BP and a significant decrease in finger flow were noted by the first time point (5 min). Within 15 min, cocaine induced a 36% +/- 5% increase in BP and a 73% +/- 18% decline in finger flow (P < 0.05 for difference between percent change in BP and percent change in flow). Dinamapsystolic and Dinamapdiastolic returned to within 15% of baseline within 30 min, while finger flow remained more than 50% below baseline for the remainder of the 60-min study period (P < 0.05). Changes in heart rate paralleled those in BP. Except for isolated cases of documented coronary vasoconstriction in patients presenting with complications after cocaine use, this study is the first to document the persistence of cocaine-induced vasoconstriction of a sensitive vascular bed beyond the hypertensive response. It thus helps to explain the development of ischemic injury after cocaine use despite a stable rate-pressure product. (Anesth Analg 1997;84:46-50)