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At least 1,009 records · Page 56Linked to original sources
PubMed1990

Dissociation of gastric acid and pepsinogen secretion in response to mercaptomethylimidazole--a new secretory compound.

Mercaptomethylimidazole (MMI), a potent antithyroid drug of the thionamide group, induces both acid and pepsinogen secretion independently in control and pylorus ligated mice. The effect is dose dependent and the drug is more effective than histamine, carbachol or isoproterenol when administered by an intraperitoneal route. MMI-stimulated pepsinogen secretion could be dissociated from the acid secretion by the use of cimetidine and omeprazole which effectively block the acid secretion without affecting the pepsinogen output. Neither acid nor pepsinogen secretion by MMI is inhibited by atropine indicating a lack of muscarinic receptor involvement in both of the processes. Nifedipine and verapamil, the calcium antagonists, by inhibiting the MMI-induced acid secretion can also dissociate pepsinogen secretion from the acid secretion. Clonidine, an alpha 2-agonist, and hexobarbital, a membrane active barbiturate, also inhibit acid secretion without affecting the pepsinogen output. These data indicate that MMI induces pepsinogen secretion independent of acid secretion. Furthermore, MMI-stimulated acid secretion is not additive with that of the histamine indicating same site (H2-receptor) of action while its synergistic effect in presence of carbachol (muscarinic receptor) indicates different site of interaction of the two compounds. On the other hand, an additive effect of MMI and carbachol on pepsinogen secretion indicates that while the carbachol effect is mediated through the muscarinic receptor, MMI stimulates pepsinogen secretion through some still unknown mechanism.

Animals↗
PubMed1983

Partial characterization of a barbiturate-induced cytochrome P-450-dependent fatty acid monooxygenase from Bacillus megaterium.

A soluble cytochrome P-450-dependent fatty acid monooxygenase activity obtained from Bacillus megaterium ATCC 14581 can be induced by at least 13 different barbiturates. In general, the potency of these compounds as inducers increases with their increasing lipophilicity. We have now shown that at least 4 of these barbiturates (phenobarbital, secobarbital, pentobarbital and methohexital) seem to induce the same active cytochrome P-450-containing enzyme by a non-substrate type mechanism. The partially purified enzymes obtained from cultures induced with each of the 4 barbiturates tested were all of similar molecular size (Mr = 130,000 +/- 10,000) and had similar turnover numbers (1400-1800 +/- 300) with either palmitoleate or myristate as substrates. None of the tested barbiturates served as substrates, activators or inhibitors of any of the monooxygenase preparations, nor did they appear to interact in any way with the monooxygenase enzyme or the P-450 component.

Bacillus megaterium↗
PubMed1983

Reassessment of brain free fatty acid liberation during global ischemia and its attenuation by barbiturate anesthesia.

We previously reported that whole-brain free fatty acids (FFA) rose almost linearly for up to 1 h after decapitation of unanesthetized rats and was significantly attenuated by pentobarbital anesthesia. However, our values for total FFA and arachidonic, stearic, oleic, and palmitic acids were severalfold higher than those obtained by previous investigators. Based upon the suggestion that this may be due to FFAs released from di- and triglycerides in the quantitation of FFAs, we have now analyzed and improved our procedures for TLC separation of FFA and reassessed the accumulation of FFA in whole brain during decapitation ischemia in unanesthetized and pentobarbital-anesthetized rats. FFA levels in whole brain after 0.5 min of ischemia were one-half to one-fourth the levels previously reported after 1 min of ischemia. The rise in FFA between 0.5 and 60 min of ischemia was 9-fold for total FFA, and between 7 and 12-fold for each of the FFAs quantitated. Pentobarbital significantly attenuated the rise of all FFAs with, however, greater effects on oleic and palmitic acids than previously reported.

Anesthesia↗
PubMed1985

Comparison of the effects of diphenylbarbituric acid, phenobarbital, pentobarbital and secobarbital on GABA-mediated inhibition and benzodiazepine binding.

We utilized biochemical and electrophysiological methods to compare the effects of anesthetic and anticonvulsant barbiturates on gamma-aminobutyric acid (GABA) receptor-coupled responses. Biochemical analysis involved barbiturate regulation of the affinity of a radiolabeled benzodiazepine for benzodiazepine receptors. The electrophysiological method involved regulation of somatic recurrent inhibition of CA1 pyramidal cells in the hippocampal slice preparation. We found that anesthetic (secobarbital and pentobarbital) but not anticonvulsant (phenobarbital and diphenylbarbituric acid) barbiturates significantly enhanced GABA receptor-coupled responses in both the biochemical and electrophysiological preparations. The results indicate that the anticonvulsant actions of barbiturates may not depend on their ability to enhance GABAergic neuronal activity.

Animals↗
PubMed1986

Effects of gamma-aminobutyric acid (GABA) receptor agonists on the neurotoxicity and anticonvulsant activity of barbiturates in mice.

The effects of gamma-aminobutyric acid (GABA) receptor agonists [4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-ol THIP]; [progabide and baclofen] on the minimal neurotoxicity and anticonvulsant activity of pentobarbital and phenobarbital in mice were investigated. When either progabide, THIP or baclofen were administered with pentobarbital, the components of this combination interacted additively by the rotorod test. Combinations of pentobarbital and progabide or phenobarbital and progabide interacted additively when subjected to the pentylenetetrazol (PTZ) minimal threshold seizure (clonic) test. THIP, even at toxic doses, did not alter the anti-PTZ activity of either pentobarbital or phenobarbital. In contrast, baclofen at toxic doses potentiated the anti-PTZ activity of pentobarbital and phenobarbital. Combinations of progabide and pentobarbital or progabide and phenobarbital interacted additively by the maximal electroshock seizure (MES) test. THIP, even when given in toxic doses, had no effect on the anti-MES activity of pentobarbital and phenobarbital. However, baclofen at nontoxic doses potentiated the anti-MES activity of phenobarbital but not that of pentobarbital. These results suggest that 1) in vitro interactions between barbiturates and GABAa receptor agonists may not be the same in vivo, 2) GABAa receptors may play a minor role in the minimal neurotoxicity and anticonvulsant activity of barbiturates and 3) inhibition of glutamate-induced excitation by baclofen may be an important action in potentiating the anti-MES activity of phenobarbital.

Animals↗
PubMed1999

Comparison of the effects of convulsant and depressant barbiturate stereoisomers on AMPA-type glutamate receptors.

BACKGROUND: Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type glutamate receptors mediate fast excitatory synaptic transmission in the central nervous system. Although barbiturates have been shown to suppress the AMPA receptor-mediated responses, it is unclear whether this effect contributes to the anesthetic action of barbiturates. The authors compared the effects of depressant [R(-)] and convulsant [S(+)] stereoisomers of 1-methyl-5-phenyl-5-propyl barbituric acid (MPPB) on the AMPA and gamma-aminobutyric acid type A (GABA(A)) receptor-mediated currents to determine if the inhibitory effects on AMPA receptors correlate to the in vivo effects of the isomers. METHOD: The authors measured whole-cell currents in the rat cultured cortical neuron at holding potential of -60 mV. Kainate 500 microM was applied as the agonist for AMPA receptors. Thiopental (3-300 microM), R(-)-MPPB or S(+)-MPPB (100-1,000 microM) was coapplied with kainate under the condition in which the GABA(A) receptor-mediated current was blocked. Effects of MPPB isomers on the current elicited by GABA 1 microM were studied in the separate experiments. RESULTS: Thiopental inhibited the kainate-induced current reversibly and in a dose-dependent manner, with a concentration for 50% inhibition of 49.3 microM. Both R(-)-MPPB and S(+)-MPPB inhibited the kainate-induced current with a little stereoselectivity. R(-)-MPPB was slightly but significantly more potent than S(+)-MPPB. In contrast, R(-)-MPPB enhanced but S(+)-MPPB reduced the GABA-induced current. CONCLUSIONS: Both convulsant and depressant stereoisomers of the barbiturate inhibited the AMPA receptor-mediated current despite of their opposite effects on the central nervous system in vivo. Although thiopental exhibited a considerable inhibition of AMPA receptors, the results suggest that the inhibition of AMPA receptors contributes little to the hypnotic action of the barbiturates.

Animals↗
PubMed1976

Bile-acid metabolism and the liver.

Primary bile acids are exclusively synthesize, and all bile acids are conjugated, in the liver. When hepatic function is altered by disease, not surprisingly the bile-acid metabolism reflects this change. 1. In chronic liver disorders the glycine: taurine ratio of serum and bile is reduced. 2. In cases of relapsing acute hepatitis and relapsing chronic active hepatitis the serum bile acids are increased, providing an aid to early diagnosis. Their pattern often distinguishes chronic cholestatic conditions from Laennec's cirrhosis. 3. In chronic liver disease, the concentration of intraduodenal bile acids is reduced; when the reduction is severe, this probably accounts for co-existent steatorrhoea. 4. In Laennec's cirrhosis, both the synthesis and pool size of cholic acid are markedly depressed; in primary biliary cirrhosis, however, preliminary data indicate a decrease in the chenodeoxycholic acid component.

Barbiturates↗
PubMed1977

Ventilation and acid-base changes in deep coma due to barbiturate or tricyclic antidepressant poisoning.

Forty-two adults in deep coma due to uncomplicated overdosage with barbiturates or tricyclic antidepressants were studied to determine the effects of the drugs and the depth of coma on ventilation and acid-base balance. All the patients were breathing spontaneously. The usual acid-base disturbance was a mixed respiratory and metabolic acidosis. No differences in effects of barbiturates and tricyclic antidepressants could be demonstrated in either grade of coma studied. Patients who were completely unresponsive to painful stimuli were significantly more acidemic (arterial [H+] 51.4 nmole/liter c.f. 44.4 mole/liter) and hypoxic (PaO2 6.6 kPa c.f. 10.5 kPa) than those who showed a minimal response to pain. These findings could not be explained by differences in alveolar ventilation, and it is suggested that they are due to ventilation/perfusion imbalance.

Acid-Base Imbalance↗
PubMed1988

Anticonvulsive activity of several excitatory amino acid antagonists against barbital withdrawal-induced spontaneous convulsions.

Several excitatory amino acid antagonists were tested for an ability to prevent spontaneous convulsions seen during the barbital abstinence syndrome in rats. Barbital-dependent animals were continuously infused intracerebroventricularly (i.c.v.) for the first 48 h following barbital withdrawal with either saline, 2-amino-7-phosphonoheptanoic acid (APH), magnesium sulfate, glutamyldiethyl ester (GDEE) or cis-2,3-piperidine dicarboxylic acid (PDA) using the highest dosages which did not affect normal behavior of the rats. All animals were observed continuously from 12 to 48 h postwithdrawal and the number of spontaneous convulsions observed in each animal was recorded. After this time, animals were killed by focused microwave irradiation and the cerebellas were collected for determination of cyclic guanosine monophosphate (cGMP) levels. While both APH and MgSO4 dramatically prevented convulsions, only APH prevented the withdrawal-induced elevation of cerebellar cGMP. PDA and GDEE had no statistically significant effect on either cerebellar cGMP levels or on convulsive activity. Although the effect of GDEE was not statistically significant, the number of convulsions was reduced to 1/3 those seen in control animals. These data implicate N-methyl-d-aspartate (NMDA) receptor-mediated pathways in seizure activity associated with the barbital abstinence syndrome and show that the withdrawal-induced elevation of cerebellar cGMP can occur without the induction of convulsions.

Amino Acids↗
PubMed1995

Effects of anaesthetic agents on basal and histamine-stimulated acid secretion in the fistula rat.

OBJECTIVES: Anaesthetized rats or surgically modified preparations such as the Shay rat are widely used to study upper gastrointestinal function in the laboratory. Despite the existence of reports demonstrating that agents such as barbiturates can influence acid output, a systematic study of the effects of anaesthetics on gastric secretion has not been undertaken. METHODS: Basal and histamine-stimulated acid output were measured in chronic fistula rats after administration of injectable and volatile anaesthetics frequently used in studies of gastric secretion in anaesthetized animals. With the exception of ether, for which recovery is very rapid, sedating rather than full anaesthetic doses were used. RESULTS: Chloralose (40 mg/kg) had no significant effect on gastric secretion. Pentobarbitone (25 mg/kg) inhibited basal and histamine-stimulated acid output, but the effect was relatively short-lived and secretion returned to control levels after 2 h. Urethane (750 mg/kg) markedly inhibited basal acid output and abolished the secretory response to histamine given 15 to 60 min later. The effects of urethane on acid secretion persisted for the entire 3 h duration of experiments, during which time basal acid output declined to levels observed in fully anaesthetized rats given 1.5 g/kg. Full anaesthesia with ether for 60 min also caused profound inhibition of basal secretion and, like urethane, abolished the effect of histamine despite the fact that the animals recovered consciousness within 5 min. CONCLUSIONS: The differential activity of anaesthetics and profound antisecretory activity of ether and urethane should be taken into account when studying gastrointestinal function and mucosal ulceration in anaesthetized animals.

Anesthetics, Intravenous↗
PubMed1975

The direct gas chromatographic analysis of barbiturates as their sodium salts.

The addition of formic acid to the carrier gas will permit the on-column liberation of the free acids following the direct injection of barbiturates as their sodium salts. These free acids may then be resolved upon an Apiezon L column: the presence of formic acid also minimizes the adsorption effects which may be associated with the gas chromatographic analysis of these relatively polar drugs.

Barbiturates↗