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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Morphine, the prototype mu opiate receptor agonist, decreased the spontaneous and [D-Ala2]-Met-enkephalinamide (DALA)-induced myoclonic contractions (MC) of submandibular muscles in the anaesthetized rat. The proposed kappa receptor agonists ketocyclazocine, ethylketocyclazocine and bremazocine failed to induce MC. In addition, bremazocine inhibited the spontaneous and DALA induced MC. Cyclazocine, the so-called sigma opiate receptor agonist, had a weak potency in generation of MC, but without step dose response tendency. The most potent opioid peptide in inducing the MC and electrocortical (ECoG) epileptic pattern was the delta opiate receptor agonist [D-Ala2,D-Leu5]-enkephalin (DADL). All drugs were administered intraventricularly. The results indicate that myoclonic phenomena induced by DADL and probably by other endopioids are mediated by delta opiate receptors in the rat brain. It is suggested that the combined ECoG and EMG method used in this study offers an opportunity to define further the biological role of opiate receptors and to identify the potential delta opiate receptor acting drugs, which might provide a new approach to the therapy of some seizure disorders.
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PMID:Delta opiate receptors are involved in the endopioid-induced myoclonic contractions. 627 61

The respiratory depression induced by two mu-opiate agonists morphine and Tyr-D-Ala-Gly-N-Me-Phe-Met(O)-ol (FK-33824), and two delta-agonists Tyr-D-Ala-Gly-Phe-D-Leu (DADLE) and Tyr-D-Ser-Gly-Phe-Leu-Thr (D-Ser2-Thr6) was studied in rats by using the intracerebroventricular route. The four opioids caused a dose-dependent depression of respiratory frequency down to apnea but high doses of morphine elicited motor activation and seizure activity. FK-33824 was the most potent, followed by DADLE, D-Ser2-Thr6 and morphine. The in vivo apparent pA2 values were determined for naloxone against FK-33824, DADLE and D-Ser2-Thr6. The pA2 value of naloxone interacting with the mu-agonist FK-33824 was significantly lower than those obtained against the two delta-agonists. It is proposed that different types of opiate receptors are involved in the opiate-induced respiratory depression.
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PMID:Interaction of naloxone with mu- and delta-opioid agonists on the respiration of rats. 630 57

Cortical application of morphine (25, 100 and 400 micrograms) induced cortical spikes in a dose-related fashion and, at 400 micrograms, behavioral and electrographic seizures. These electrographic seizures were not opiate specific since this activity occurred undiminished in naltrexone-pretreated animals and was even potentiated in animals pretreated for 6 days with increasingly higher doses of systemic morphine. In contrast to the effects induced by morphine, the most consistent electrographic effect of cortically applied D-Ala2-methionine-enkephalin (DALA) and methadone was a depression of cortical EEG. These results support the hypothesis that the cortex and spinal cord together form the anatomical substrate of the documented nonspecific convulsive action of high systemically administered doses of morphine.
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PMID:Nonspecific convulsions are induced by morphine but not D-Ala2-methionine-enkephalinamide at cortical sites. 632 65

The relationship between deprenyl (MAO-B inhibitor), beta-phenylethylamine (PEA, MAO-B substrate) and [D-Ala2]-Met-enkephalinamide (DALA)-induced seizure was studied in the urethane-anaesthetized rats. A combined electromyographic (EMG) and electrocorticographic (ECoG) method was used. PEA (20-100 micrograms ivt) or DALA (10 micrograms ivt) induced myoclonic contractions (MC) in the submandibular muscle and epileptiform pattern with spike activity in the ECoG. Administration of subconvulsant doses of PEA (5-10 micrograms ivt 0.5-1 min before DALA) significantly increased DALA-induced seizure activity. Similarly, blockade of MAO-B with deprenyl (3-48 mg/kg ip) also enhanced DALA-induced epileptiform pattern. It is evident from this study that MAO-B system significantly modulates the excitatory phenomena induced by DALA. These findings of interactions between MAO-B system and enkephalinergic one, might be of relevance in the clinical situations such as psychosis, stress, a use of tricyclic antidepressants and all other cases, where the alteration of MAO-B system is a part of disease or induced during drug therapy.
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PMID:MAO-B inhibitor deprenyl and beta-phenylethylamine potentiate [D-ALA2]-Met-enkephalinamide-induced seizures. 640 86

A brief review of the neurochemical effects of the convulsant agent L-methionine-dl-sulfoximine (MSO) on cerebral methylation reactions is presented. Our findings point to the involvement of a number of endogenous methyl acceptor molecules, including histamine, membrane phospholipids, and membrane proteins, in the mediation of the convulsant effect. Our findings also associate the inhibition of methylations by high levels of S-adenosyl-L-homocysteine in brain with protection against MSO-induced seizures. We propose that MSO acts by eliciting the acceleration of a regulatory methylation-demethylation sequence at key molecular sites, including the benzodiazepine receptor complex, which creates an imbalance in this sequence's normal mediation of convulsant-anticonvulsant mechanisms.
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PMID:Brain methylation and epileptogenesis: the case of methionine sulfoximine. 650 48

A child with intractable seizures from the age of 10 months and developmental retardation developed jaundice and hepatosplenomegaly at 23 months. She died at the age of 25 months. Methionine and tyrosine were elevated in urine, plasma, CSF, and brain. These elevations were more marked in the CNS than in the blood. 4-Hydroxyphenylpyruvate dioxygenase, an enzyme involved in the metabolism of tyrosine, was undetectable in skin fibroblasts and liver. This finding together with other biochemical data suggest that our case had an inherited disorder of tyrosine metabolism, in the category of tyrosinemia I. Disturbances of tyrosine and methionine metabolism in the CNS in tyrosinemia I may be more important than has been realized. The disorder should be considered in children with unexplained epilepsy and in those who develop hepatic dysfunction while on anticonvulsants.
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PMID:Tyrosinemia and intractable seizures. 661 Dec 56

Twenty-three substituted 3,4-dihydro-4-oxoquinazolines or 3,4-dihydro-4-oxoazaquinazolines have been synthesized utilizing 2-amino-3-cyano-4,5-dimethylfuran and methyl acrylate as precursors for synthesis of the required substituted anthranilates. Six additional azaquinazolones were synthesized from 2-aminonicotinic or 3-aminopicolinic acid for comparison studies. All compounds were evaluated in mice with the maximal electroshock (MES) seizure and pentylenetetrazol (sc Met) seizure threshold tests for potential anticonvulsant activity and in the rotorod test to evaluate neurotoxicity. Nine of the twenty-nine compounds in the series demonstrated anticonvulsant action. The azaquinazolones were found to possess the most significant activity.
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PMID:Synthesis of 3,4-dihydro-4-oxoquinazoline derivatives as potential anticonvulsants. 662 Mar 1

An intraventricular pulse of [14COOH]L-methionine to mice pretreated with the convulsant L-methionine-dl-sulfoximine (MSO) resulted in significantly higher than control specific radioactivity values of cerebral [14COOH]L-methionine (Met), [14COOH]S-adenosyl-L-methionine (AdoMet) and [14COOH]S-adenosyl-L-homocysteine (AdoHcy). MSO administration (3 hr) also decreased brain steady-state levels of Met, AdoMet, and AdoHcy. Following an intraventricular pulse of [3H-methyl]L-methionine, the levels of [3H-methyl]phosphatidylmonomethylethanolamine and of membrane associated and soluble [3H-methyl]carboxylmethylated proteins were increased over corresponding saline-treated controls. The activity of cerebral histamine N-methyltransferase was also increased after MSO treatment. The administration of a combination of adenosine and homocysteine thiolactone to MSO-pretreated animals counteracted the MSO-induced decreases in brain Met, AdoMet, and AdoHcy as well as the increase in histamine N-methyltransferase activity. In addition, administration of adenosine together with homocysteine thiolactone decreased the incidence of, and increased the latency to MSO seizures, with the most effective anticonvulsant action occurring when cerebral AdoHcy levels were at their highest.
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PMID:Possible role of increased brain methylation in methionine sulfoximine epileptogenesis: effects of administration of adenosine and homocysteine thiolactone. 666 52

We have proposed that glutamine serves in a facilitated diffusion process, mediated by the enzyme gamma-glutamyl transferase (gamma-glutamyl transpeptidase; gamma GT) and that it leaves the brain in exchange for entering amino acids. Glutamine is also a precursor of gamma-aminobutyric acid (GABA). Thus, providing an alternate substrate for gamma GT should spare brain glutamine, raise GABA, and cause an anticonvulsant effect. We have found that glycylglycine, the best-known substrate for gamma GT, and delta-aminovaleric acid (DAVA), a structural analog, have anticonvulsant activity in DBA/2J mice. Both compounds can decrease the incidence and severity of seizures induced by L-methionine-RS-sulfoximine or electroconvulsive shock. DAVA was also tested and found to be active against seizures caused by pentylenetetrazol or picrotoxin. [14C]DAVA entered the brain at the rate of 18.7 nmol/g/min. The activity of DAVA as a substrate of gamma GT was intermediate to that of glycylglycine and glutamine. Preliminary studies have shown that brain glutamine and perhaps GABA are elevated 3 h after administration of DAVA (7.5 mmol/kg). These findings support the theory that glutamine exchange plays a role in amino acid transport across the blood-brain barrier and suggests a new concept in anticonvulsant therapy.
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PMID:Anticonvulsant activity of glycylglycine and delta-aminovaleric acid: evidence for glutamine exchange in amino acid transport. 683 37

In unrestrained rabbits with generalized epileptic seizures induced by systemic application of convulsant drugs, regional changes in blood-brain barrier (BBB) permeability to macromolecules were investigated using Evans Blue (EB) as indicator. BBB leakage due to seizures was present only in animals in which the mean arterial blood pressure rose about 50 mm Hg with the onset of convulsive motor activity. However, a blood pressure increase was not necessarily associated with the occurrence of BBB opening. Pentylenetetrazole-induced seizures resulted in bilateral EB leakage mainly in the hypothalamus, with exception of the mammillary bodies, and the preoptic area, and they were associated, in most cases, with an intensive staining of the cerebellum and also of the midbrain tegmentum. In contrast, seizures due to the GABA receptor blocker bicuculline brought about a penetration of the dye in the region of the pallidum, whereas the GABA synthesis inhibitor methoxypyridoxine produced BBB breakdown in the hippocampus. Methionine-sulfoximine convulsions resulted in a selective stain of the corpora mammillaria, and kainic acid induced a diffuse leakage in neocortical brain areas. As a rule, BBB breakdown was bilateral and confined to anatomically limited brain areas, suggesting that BBB integrity was not only disturbed by abrupt increases in the intraluminal pressure, but was also influenced from the brain tissue. The fluorescence microscopic observations revealed that the tracer penetrated into the neuropil through larger vessels. It had the tendency to accumulate in neurons. In case of the hippocampus, CA2 pyramidal cells revealed more intense uptake of EB than those of the adjacent fields.
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PMID:Regional patterns of blood-brain barrier breakdown during epileptiform seizures induced by various convulsive agents. 687 4


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