Showing papers on "Barbiturate published in 1977"

Phenobarbital actions in vivo: effects on extra cellular potassium activity and oxidative metabolism in cat cerebral cortex.

Abstract: Extracellular potassium activity and changes in the reduction levels of intramitochondrial pyridine nucleotide (NAD) and cytochrome-a,a3 were monitored in the cerebral cortex of cats at rest and during electrical stimulation, before and after administration of sodium phenobarbital. Stimulation of the cortical surface evoked a transient increase in the level of oxidized NAD which was proportional in magnitude to the associated transient elevation of extracellular potassium. Phenobarbital (i.v.) produced, within minutes, a persistent shift in NAD to a more reduced level indicative of decreased oxygen consumption. Electrical excitability of the cortex also decreased within minutes, although there was no concomitant change in the resting extracellular potassium activity. Cortical stimulation produced transient elevations of [K+]0 and NADH oxidation and these responses returned to base lines more slowly following the barbiturate administration. However, the proportionality between NADH oxidation and [K+]0 elevation was not altered by phenobarbital. The kinetics of the cytochrome-a, a3 response to cortical stimulation mirrored those of NADH, implying that phenobarbital was not blocking electron transport in the respiratory chain between NADH and cytochrome-a, a3 even at doses where "resting" tissue oxygen consumption was decreased. The prolongation of recovery metabolism following phenobarbital was interpreted as being the result of protracted elevation of extracellular potassium activity. The slow return to "resting" levels of extracellular potassium is probably caused by interference with passive clearance mechanisms.

Thyrotropin-releasing hormone: physiological concomitants of behavioral excitation.

Abstract: Two doses (10 microng and 100 microng) of thyrotropin-releasing hormone (TRH) or saline were injected intraventricularly in rabbits pretreated with either saline, pentobarbital or phenobarbital. Behavior, EEG patterns, respiration rate and heart rate were monitored for 100 min posttreatment. TRH significantly altered all physiological indices except heart rate in both barbiturate- and saline-pretreated animals. The results support the contention that TRH modified central functioning by direct action. Results are discussed in terms of barbiturate antagonism and excitatory effects of TRH.

Some observations on the mechanism of benzodiazepine-barbiturate interactions in the mouse.

Abstract: 1 The prolongation of pentobarbitone sleeping by five benzodiazepines, administered by prior intraperitoneal injection, was measured in mice. The pentobarbitone was injected either intraperitoneally or intracerebroventricularly. For each benzodiazepine, the prolongation was dose-related and differences in potency between benzodiazepines were not marked. 2 The percentage prolongation of sleeping times produced by most of the benzodiazepines was greater when the pentobarbitone was given intracerebroventricularly and was explained by a preferential addition of CNS depressant effects associated with this route. 3 To test whether the action of intraperitoneally administered pentobarbitone had been influenced by a metabolic component, the effects of nitrazepam on drug metabolism, measured by changes in plasma phenazone levels in the mouse, were studied. Nitrazepam (32 mg/kg, i.p.) produced a 23% reduction in the rate of phenazone metabolism. 4 Nitrazepam was also shown to have produced a transient fall in body temperature. Calculations based on Q10 values suggested that this hypothermia accounted, at most, for half the metabolic change measured.

gamma-aminobutyric acid in alcohol, barbiturate and morphine dependence: a review.

Abstract: The literature on the γ-aminobutyric acid system in acute and chronic effects of alcohol, barbiturates and morphine is reviewed. Results are conflicting and in the light of present knowledge of the nervous system there is no evidence to date which would implicate disturbance of the γ-aminobutyric acid system as having a causal role in the genesis or maintenance of alcoholism or other drug dependent states.

Barbiturate-Induced Choleresis: Possible Independence from Microsomal Enzyme Induction

Abstract: The influence of four barbiturates, phenobarbital, barbital, thiopental, and pentobarbital, on bile secretion and on the hepatic microsomal system was studied in anesthetized rats. The barbiturates were injected intraperitoneally for 4 days and the animals were studied on the 5th day. It was found that: (1) phenobarbital, barbital, and thiopental, but not pentobarbital, significantly increased liver weight, cytochrome P-450 concentration in the liver, decreased pentobarbital sleeping time and induced a hypertrophy of the smooth endoplasmic reticulum in the hepatocytes at electron microscopy; (2) in contrast, the four barbiturates, including pentobarbital, significantly increased bile flow; this increase was attributed to an increase in the bile acid independent bile flow. There was no correlation between the increase in bile flow and the cytochrome P-450 concentration in the liver. It is concluded that the increase in bile flow observed after barbiturate treatment in the rat is possibly independent of the hepatic microsomal enzyme induction produced by these drugs.

Alteration of Hepatic microsomal enzyme systems and the lethal action of non-steroidal anti-arthritic drugs in acute and chronic models of inflammation.

Abstract: Depression of the hepatic microsomal enzyme system(s) in adjuvant-induced polyarthritis (AIP), a chronic inflammation model, has been confirmed indirectly by the enhancement of hexobarbital Na-induced sleeping time and extended for the first time to zoxazolamine-induced paralysis. In addition, barbital Na-induced anesthesia was increased during the course of AIP development, indicating that the CNS of these rats appears to be more sensitive to drug effects, since this barbiturate is excreted virtually unmetabolized. Most likely because of these effects, LD50 values for acetylsalicylic acid, phenylbutazone and indomethacin in AIP rats decreased in terms of mg/kg (increased toxicity) as the disease became more severe (Day 21) since they are known ultimately to be metabolized by the liver. On the other hand, the toxicity of a new non-steroidal anti-inflammatory agent, meseclazone, was not altered significantly in AIP. This is most likely due to the fact that its near total conversion to 5-chlorosalicylic acid has been shown to occur by hydrolytic cleavage as it passes through the intestinal wall with little hepatic involvement. Finally, carrageenan edema, a model of acute inflammation, did not affect barbiturate sleeping times or zoxazolamine paralysis, nor were any of these drugs studied more lethal in this disease state.