Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Cyclohexanecarboxylic Acids”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,117 records · Page 62Linked to original sources
PubMed1982

Effect of fibrinolysis inhibitor and chemotherapeutics on the growth of human cancers transplanted into nude mice and in tissue culture.

Effects of tranexamic acid (AMCHA) alone or together with anticancer drug on the growth of human cancers transplanted into nude mice and in tissue culture were investigated. AMCHA showed no effects on cancer cells in vitro. Fibrin deposition and host stromal reaction at the advancing border of the tumor tended to increase after AMCHA administration. These seem to contribute to the significant reduction of tumor growth rate by AMCHA in combination with an anticancer drug compared to control.

Animals↗
PubMed1977

The effect of fibrinolytic inhibition in the resolution of experimental vitreous hemorrhage.

Complete inhibition of vitreous fibrinolytic activity with 4-amino-methylcyclohexane carbonic acid was associated with significantly delayed resolution of vitreous hemorrhages in rabbits. However, polyacrylamide gel electrophoresis indicated but a slight delay in the removal of the fibrin component of vitreous clots, and most of the residual vitreous opacity comprised intact red blood cells. Fibrin degradation products may act as chemotactic agents, promoting the removal of red blood cells by leukocytes; hence, their absence in treated rabbits might explain in part the delayed red blood cell clearance.

Absorption↗
PubMed1989

Tranexamic acid for control of haemorrhage in acute promyelocytic leukaemia.

In a double-blind study, 12 consecutive patients with acute promyelocytic leukaemia were randomised either to tranexamic acid (TA group) or to placebo (control group) for 6 days to see whether inhibition of fibrinolysis would reduce haemorrhage and transfusion requirements. The total study period was 14 days. In the TA group, there were fewer haemorrhagic episodes, as determined by a scoring system. Packed red cell transfusion requirements decreased; and fewer additional platelet concentrate transfusions were needed. These beneficial effects were more pronounced in the second week. There were no thromboembolic complications.

Adolescent↗
PubMed2004

Dual effects of gabapentin and pregabalin on glutamate release at rat entorhinal synapses in vitro.

We have recently shown that the anticonvulsant drugs phenytoin, lamotrigine and sodium valproate all reduce the release of glutamate at synapses in the entorhinal cortex in vitro. In the present investigation we determined whether this property was shared by gabapentin and pregabalin, using whole-cell patch-clamp recordings of excitatory postsynaptic currents (EPSCs) in layer V neurons in slices of rat entorhinal cortex. Both drugs reduced the amplitude and increased the paired-pulse ratio of EPSCs evoked by electrical stimulation of afferent inputs, suggesting a presynaptic effect to reduce glutamate release. The frequency of spontaneous EPSCs (sEPSCs) was concurrently reduced by GBP, further supporting a presynaptic action. There was no significant change in amplitude although a slight reduction was seen, particularly with gabapentin, which may reflect a reduction in the number of larger amplitude sEPSCs. When activity-independent miniature EPSCs were recorded in the presence of tetrodotoxin, both drugs continued to reduce the frequency of events with no change in amplitude. The reduction in frequency induced by gabapentin or pregabalin was blocked by application of the l-amino acid transporter substrate l-isoleucine. The results show that gabapentin and pregabalin, like other anticonvulsants, reduce glutamate release at cortical synapses. It is possible that this reduction is a combination of two effects: a reduction of activity-dependent release possibly via interaction with P/Q-type voltage-gated Ca channels, and a second action, as yet unidentified, occurring downstream of Ca influx into the presynaptic terminals.

Amines↗
PubMed1975

Effect of triphenylmethane derivatives on cell-free macromolecular synthesis. I. Aminoacyl-tRNA synthetase.

The inhibitory effect of aurintricarboxylic acid (ATA) on phenylalanyl-tRNA synthetase is demonstrated in the rabbit-reticulocyte system. This inhibition is not specific to ATA; other triphenylmethane derivatives are also potent inhibitors of this enzyme reaction. The site of inhibitory action is in the enzyme itself, not in the tRNA molecule. It thus appears that the skeletal structure of ATA, not the side chains, is responsible for its inhibitory action, and that ATA is a nonspecific inhibitor of the reactions involving polynucleotides.

Amino Acyl-tRNA Synthetases↗
PubMed1986

Biochemical effects and monitoring of exposure of rats to 4-methylcyclohexyl-1,6-dicarboxylic acid anhydride vapour.

Male Wistar rats exposed to 5, 10 or 20 p.p.m. 4-methylcyclohexyl-1,6-dicarboxylic acid anhydride vapour for 2-11 weeks showed dose-dependent blood anhydride concentrations. The maximum concentrations were found after two weeks. At five exposure weeks, they were smaller but they did not decrease further thereafter. The change was coincident with increased epoxide hydrase activity in liver. The excretion of 4-methylcyclohexyl-1,6-dicarboxylic acid was detected in the urine. The excretion was linearly related to the exposure in specimens collected during the 10th and 11th week. Brain acetylcholinesterase activity was transiently inhibited by the exposure at the two higher doses while decreased enzyme activity in the isolated spinal cord axons was only found after 11 weeks. This change was simultaneous with increased creatine kinase activity in the cerebellar homogenate. In the occupational setting, acetylcholinesterase activity might only be significantly inhibited in lungs because of the low exposure levels.

Acetylcholinesterase↗
PubMed1996

Reductive metabolism and its role in the disposition of the hydroxamic angiotensin-converting enzyme inhibitor idrapril calcium in rat.

1. The metabolism of 14C-idrapril calcium, the prototype of a new class of angiotensin-converting enzyme inhibitors, was studied in rat after a single intravenous administration. Plasma, urine, faeces, and bile were assayed for total and hplc-fractionated radioactivity. 2. Only one major metabolite (M1, 2-sarcosinamide-cis-1,2-cyclohexanedicarboxylamide) was observed, along with idrapril, in plasma. Three metabolites (M1, M2, cis-1,2-cyclohexanedicarboxylic acid, and M3, a glucuronate derivative of M1) were present in 0-8-h urine, unchanged idrapril being the most abundant product. In bile, two metabolites (M1, M3), but not the parent compound, were found. 3. In conclusion intravenous idrapril undergoes hepatic reduction to M1 and hydrolysis to M2. M1 can be glucuronated to M3 and both are partially excreted in the bile and further processed in the gut to reabsorbable radioactive species.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1982

Inactivation of pyridoxal phosphate enzymes by gabaculine. Correlation with enzymic exchange of beta-protons.

Gabaculine, 5-amino-1,3-cyclohexadienylcarboxylate, is a very efficient enzyme-activated inhibitor of gamma-aminobutyrate transaminase (Rando, R. R. (1977) Biochemistry 16, 4604-4610). However, enzymes for which gamma-aminobutyrate is not a substrate are also inactivated by gabaculine. Thus, purified D-amino acid transaminase, L-alanine transaminase, and L-aspartate transaminase are also inactivated (Ki values of 0.1 mM, 1 mM, and 55 mM, respectively). The effects of this inhibitor on such a diverse group of enzymes appear to be related to the enzymic exchange of beta-protons of their normal substrates. L-Alanine transaminase and L-aspartate transaminase are known to catalyze such an exchange (Walter, U., Luthe, H., Gerhart, F., and Söling, H.-D. (1975) Eur. J. Biochem. 59, 395-403). D-Amino acid transaminase and gamma-aminobutyrate transaminase, which are inactivated by gabaculine, also catalyze exchange of the beta-protons of their substrates. Alanine racemase and tryptophanase, which are known not to catalyze an analogous exchange, were found to be insensitive to gabaculine. We postulate that aromatization of gabaculine, in which the beta-proton is removed, is an enzyme-catalyzed event for those pyridoxal phosphate enzymes that have a nucleophilic group at the active site to catalyze this process.

4-Aminobutyrate Transaminase↗
PubMed1993

Potent and stereospecific anticonvulsant activity of 3-isobutyl GABA relates to in vitro binding at a novel site labeled by tritiated gabapentin.

3-Isobutyl GABA is a derivative of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and is also structurally related to the novel anticonvulsant gabapentin. The S(+) enantiomer of 3-isobutyl GABA blocks maximal electroshock seizures in mice and also potently displaces tritiated gabapentin from a novel high-affinity binding site in rat brain membrane fractions. The R(-) enantiomer is much less active in both assays, suggesting that the gabapentin binding site is involved in the anticonvulsant activity of 3-isobutyl GABA.

Acetates↗
PubMed2000

[GABA-ergic system and antiepileptic drugs].

gamma-Aminobutyric acid (GABA) belongs to main inhibitory neurotransmitters in the central nervous system and activates three types of specific receptors--GABAA, GABAB i GABAC. At present, little is known about GABAC-mediated events. GABAB receptors are metabotropic, whilst stimulation of ionotropic GABAA receptors results in opening the chloride channel, followed by influx of chloride ions and hyperpolarization. The GABAA receptor possesses also binding sites for benzodiazepines and barbiturates which, via these sites, enhance GABAA-mediated events. Another antiepileptic drug potentiating GABA-ergic inhibition is valproate, which increases synthesis of GABA and reduces its metabolism. Among new antiepileptic drugs associated with the GABA-ergic system are tiagabine, vigabatrin, and to a certain degree--gabapentin. Tiagabine blocks neuronal and glial uptake of GABA whilst vigabatrin increases the synaptic concentration of GABA by inhibition of GABA aminotransferase. Gabapentin, probably through the activation of glutamic acid decarboxylase, leads to the increase in synaptic GABA. However, this antiepileptic drugs is also binds to specific sites within voltage-dependent calcium channels, which results in the reduced intraneuronal concentration of calcium ions. Presumably, tiagabine and vigabatrin possess only one mechanism of action, associated with the increased GABA-ergic inhibition. Although topiramate and felbamate were shown to enhance GABA-mediated events, they have additional mechanisms of action, including blockade of voltage-dependent sodium channels and inhibition of glutamatergic neurotransmission.

Acetates↗
PubMed1997

Treatment of restless legs syndrome with gabapentin.

Gabapentin is a well tolerated anticonvulsant, structurally related to gamma-aminobutyric acid, with an unknown mechanism of action. Restless legs syndrome (RLS) is a disorder characterized by sensory and motor symptoms in the legs that is best treated with dopaminergic drugs and opiates. In this open-label study, eight patients with RLS were treated with gabapentin. Four of the eight had a beneficial response, three with almost complete resolution of symptoms for up to 6 months. For a disorder that is often difficult to treat, these results are encouraging, and they suggest that a placebo-controlled trial is warranted.

Acetates↗
PubMed2002

Evidence for glucose-6-phosphate transport in rat liver microsomes.

The existence of glucose-6-phosphate transport across the liver microsomal membrane is still controversial. In this paper, we show that S3483, a chlorogenic acid derivative known to inhibit glucose-6-phosphatase in intact microsomes, caused the intravesicular accumulation of glucose-6-phosphate when the latter was produced by glucose-6-phosphatase from glucose and carbamoyl-phosphate. S3483 also inhibited the conversion of glucose-6-phosphate to 6-phosphogluconate occurring inside microsomes in the presence of electron acceptors (NADP or metyrapone). These data indicate that liver microsomal membranes contain a reversible glucose-6-phosphate transporter, which furnishes substrate not only to glucose-6-phosphatase, but also to hexose-6-phosphate dehydrogenase.

Animals↗
PubMed1983

Anticonvulsant activity of the glial-selective GABA uptake inhibitor, THPO.

The intramuscular administration of 4,5,6,7-tetrahydroisoxazolo [4,5-c] pyridin-3-ol (THPO) delayed the onset of isonicotinic acid hydrazide-induced seizures in very young chicks but not in adult mice, the difference being due to the state of development of the blood-brain-barrier which controls access of the drug to the brain tissue. THPO was also effective in preventing seizures induced in epileptic chicks by intermittent photic stimulation. The anticonvulsant action after combined administration of THPO and gabaculine, an inhibitor of GABA-alpha-oxoglutarate aminotransferase activity, was no greater than the anticonvulsant action of gabaculine alone.

4-Aminobutyrate Transaminase↗
PubMed1987

Gabapentin as an antiepileptic drug in man.

Gabapentin, 1-(aminomethyl) cyclohexane acetic acid, is a GABA analogue whose antiepileptic properties were tested in a double blind cross-over trial design as add-on therapy in a dose ranging study which compared 300 mg, 600 mg, and 900 mg/day (each dose given for 2 months) in 25 patients with severe partial and generalised epilepsies. A dose related antiepileptic effect was observed. All three doses were well tolerated and no psychometric impairment was noted. No significant drug interactions were seen. The drug appears worthy of further assessment.

Acetates↗
PubMed1991

Regulation of c- and N-myc expression during induced differentiation of murine neuroblastoma cells.

Using clones N1E-115 and N1A-103 from mouse neuroblastoma C1300, a comparative analysis of c- and N-myc gene expression was undertaken both in proliferating cells and in cultures exposed to conditions which induce differentiation. Under the latter conditions, while N1E-115 cells extend abundant neurites and express many biochemical features of mature neurons, clone N1A-103 stops dividing and expresses certain neurospecific markers but is unable to differentiate morphologically. In both clones, chemical agents, i.e. 1-methyl cyclohexane carboxylic acid (CCA) or dimethyl sulfoxide (DMSO), induce a decrease in c-myc expression. Similar results were found for N-myc gene in N1E-115 cells, but in contrast, in clone N1A-103, N-myc expression is increased with CCA and not modified with DMSO. Globally, this study favours the hypothesis that changes in c-myc expression would correspond to cell division blockade and differentiation, while modulations in N-myc are more closely related to an early phase of terminal differentiation.

Animals↗
PubMed1988

Interrelationships between ornithine, glutamate, and GABA. II. Consequences of inhibition of GABA-T and ornithine aminotransferase in brain.

The objective of the present study was to compare the effects of elevation of GABA concentration and those of inactivation of L-ornithine: 2-oxoacid aminotransferase (OAT) on the in vivo metabolism of L-ornithine (Orn) in brain. Vigabatrin (4-aminohex-5-enoic acid) and gabaculine (5-amino-1,3-cyclohexadienyl carboxylic acid), two well known inactivators of GABA-T, were used to elevate brain GABA concentrations. The latter inactivates OAT also. Transamination of Orn is, from a quantitative point of view, a significant reaction in mouse brain. GABA is a feed-back regulator of OAT. Within GABAergic neurons Orn concentration may be regulated by endogenous GABA. Extensive inactivation of OAT causes a considerable increase of Orn concentration, both in synaptosomes and in non-synaptosomal compartments. The results are compatible with a role of Orn as precursor of glutamate and/or GABA in certain neurons.

4-Aminobutyrate Transaminase↗
PubMed1971

A supernatant factor involved in initiation complex formation with eukaryotic ribosomes.

Embryos of the brine shrimp, Artemia salina, were used in a study of polypeptide chain initiation in an in vitro system from a eukaryote. A protein, isolated from the high-speed supernatant, has been highly purified and shown to have properties that suggest it is the eukaryotic equivalent of the Escherichia coli initiation factor F(2): It promotes the AUG-dependent binding of fMet-tRNA (E. coli) to the Artemia 40S ribosomal subunit, but not to either the 60S or 80S species; the bound fMet-tRNA is placed in a site on the smaller subunit from which it reacts with puromycin upon addition of the 60S subunit; and the activity is sensitive to aurintricarboxylic acid and edeine, specific inhibitors of initiation. The factor, a basic protein of molecular weight about 100,000, is inactivated by N-ethylmaleimide, an SH-binding reagent, and is clearly distinct from the Artemia elongation factors, T(1) and T(2). In addition, the factor stimulates the poly(U)-dependent binding of Phe-tRNA (E. coli) to the Artemia 40S ribosomal subunit. This reaction, though similar to the fMet-tRNA-binding reaction, differs in that the bound Phe-tRNA is largely resistant to release by puromycin.

Adenine Nucleotides↗
PubMed1981

Coagulation and fibrinolysis in blood and cerebrospinal fluid after aneurysmal subarachnoid haemorrhage: effect of tranexamic acid (AMCA).

Serial assays of blood coagulation factors as well as of fibrin/fibrinogen degradation products (FDP) and plasminogen activatory activity (PA) on fibrin plates in blood and cerebrospinal fluid (CSF) were performed in 41 consecutive patients with recently ruptured cerebral aneurysms, 21 of whom were randomly treated with tranexamic acid (AMCA). Coagulation factors were unaffected by the drug and plasminogen and FDP decreased in blood after two weeks' treatment. After one week, PA in CSF was increased in control patients and unchanged in AMCA-treated patients, whereas CSF-FDP had decreased among AMCA-treated patients. After two weeks PA as well as FDP in CSF showed the same values in both groups. An increase in CSF-FDP occurred after rebleeding and in patients with cerebral ischaemic symptoms. The results indicate that AMCA inhibits local fibrinolysis in CSF in patients with aneurysm rupture.

Adult↗