Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The action of opiate receptor agonists: (D-Ala2)-methionine enkephalinamide (D-MEA), morphine, heroin, etorphine, and antagonists: naloxone and diprenorphine on audiogenic seizures was tested during ethanol abstinence. The action of diazepam and clonidine was also tested Morphine (5 and 20 mg/kg), but not heroin and etorphine, given intraperitoneally inhibited the seizures, similarly as intraventricularly administered D-MEA did. However, morphine given by this route was ineffective. Diazepam and clonidine inhibited audiogenic seizures: the action of clonidine was counteracted by yohimbine, but not by prazosin. The results may be considered as supporting the hypothesis on the participation of opioid system in ethanol abstinence. However, the participation of gabergic and noradrenergic systems cannot be ruled out: these systems may possibly interact with the opioid system in evoking the symptoms of ethanol abstinence.
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PMID:Involvement of opioid and other systems in ethanol abstinence audiogenic seizures in the rat? 299 52

In rats the influence of the delta opioid agonists [Leu]enkephalin, [D-Ala2-D-Leu5]enkephalin, [D-Ala2]methionine enkephalinamide and synthetic analogue of [Met]enkephalin: Tyr-D-Ala-Gly-Phe-D-Leu-OMe on audiogenic seizures was tested during ethanol abstinence. All investigated drugs significantly inhibited this ethanol withdrawal symptom. The results are compatible with the hypothesis of opioid involvement in the ethanol abstinence syndrome.
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PMID:Audiogenic seizures during ethanol withdrawal can be blocked by a delta opioid agonist. 302 46

In an attempt to elucidate the relationship between endogenous methionine-enkephalin (ME) and vasoactive intestinal polypeptide (VIP) with generalized seizures, we determined regional brain levels of ME-like and VIP-like immunoreactivity (ME-LI and VIP-LI) in El mice during and after seizures induced by repeated tossing stimulation. The levels of ME-LI in the striatum and hippocampus of seizure-naive El mice (El-) were lower than those of the control ddY mice, the mother strain of El mice. Conversely, the level of VIP-LI in the medulla oblongata and pons of El- was higher than that of ddY mice. The level of ME-LI in the striatum of seizure-experienced El mice (El+) killed 96 hours after three consecutive seizures was high, while levels of VIP-LI in the striatum and hypothalamus were low, in comparison to those of El- mice. A detailed time-course study revealed that seizures in El mice caused (1) significant decreases in levels of ME-LI in the striatum and hippocampus during seizures, (2) a significant decrease of VIP-LI content in the striatum 3 hours after seizures, and (3) a significant increase in hypothalamic VIP-LI 9 hours after seizures. These observations suggest that ME and VIP may play some role in El mouse seizures.
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PMID:Differences in ME-LI and VIP-LI in discrete brain regions of seizure-naive and seizure-experienced El mice. 321 55

A number of spiro[1,3-dioxolane-2,3'-indolin]-2'-ones were synthesized and tested for anticonvulsant activity in the maximal electroshock seizure (MES) and pentylenetetrazole seizure threshold (sc-Met) tests. 5'-Chlorospiro[1,3-dioxolane-2,3'-indolin]-2'-one was the most active compound in the MES test and had ED50 = 27.97 mg/kg. Structural analogues spiro[1,3-dioxane-2,3'-indolin]-2'-one, spiro[1,3-dithiolane-2,3'-indolin]-2'-one, spiro[indoline-3,2'-[1,3]-oxathiolan]-2-one, and 3,3-dimethoxyindolin-2-one were also evaluated for anticonvulsant activity. Almost all compounds submitted for screening exhibited the ability to protect mice against electrically and chemically induced seizures. The ED50 and TD50 values for some of the title compounds are reported. Anticonvulsant screenings were carried out through NINCDS, NIH.
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PMID:Potential anticonvulsants. 11. Synthesis and anticonvulsant activity of spiro[1,3-dioxolane-2,3'-indolin]-2'-ones and structural analogues. 336 68

ADD 17014[1-(4-chlorophenyl)-5-(4-pyridyl) delta 2-1,2,3-triazoline], is a representative member of a hitherto unknown, structurally novel family of anticonvulsant agents. The anticonvulsant profile of ADD 17014 following intraperitoneal (i.p.) and oral administration in mice and rats was evaluated using a battery of well-standardized anticonvulsant tests and compared with phenytoin (PHT), phenobarbital (PB), ethosuximide (ESM), and valproate (VPA). The results indicate that ADD 17014 is effective in nontoxic i.p. doses in mice by the maximal electroshock seizure (MES), Metrazol (subcutaneous, s.c. Met), bicuculline (s.c. Bic) and picrotoxin (s.c. Pic) tests, but ineffective against strychnine-induced seizures; it is also effective after nontoxic oral doses in both mice and rats by the MES and s.c. Met tests. Protective indices (PI = TD50/ED50), calculated from i.p. data in mice, were highest for ADD 17014 by the s.c. Met (26.02) and s.c. Bic (93.93) tests; the PIs, after oral administration in mice and rats, were equal to or higher than those of the prototype agents. In vitro receptor binding studies of ADD 17014 and potential metabolites indicated no significant inhibitory activity except for the beta-amino alcohol, which displaced almost 93% of [3H]glutamate from the glutamate receptors, suggesting that ADD 17014 may be functioning as a prodrug and an excitatory amino acid antagonist. The overall results indicate that ADD 17014 is a relatively nontoxic agent that more closely resembles PB and VPA, with a broad and unique spectrum of anticonvulsant activity.
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PMID:Triazolines XV. Anticonvulsant profile of ADD 17014, a potentially unique 1,2,3-triazoline antiepileptic drug, in mice and rats. 337 Dec 87

The biosynthesis and posttranslational processing of proenkephalin and the level of preproenkephalin mRNA were investigated in the mossy fiber system of the granule cells of the hippocampus in the presence or absence of a unilateral lesion of the hilus, a procedure that produces an episode of recurrent bilateral hippocampal seizures lasting several hours. Both immunocytochemistry and radioimmunoassay (RIA) have demonstrated that the hilus lesion leads to large bilateral increases in enkephalin immunoreactivity in the mossy fiber system. In the present study, RIA data indicate that following an initial decline in immunoreactivity, enkephalin content within the mossy fibers first begins to increase between 18 and 24 hr after lesioning. Using the technique of in vivo radiolabeling and high-performance liquid chromatographic purification of identified radiolabeled peptides, we observed a 14-fold increase in incorporation of radiolabeled methionine into Met5-enkephalin at 24-30 hr postlesion, as compared with control animals, when Met5-enkephalin was purified from the mossy fiber terminal fields. To examine the posttranslational proteolytic processing of proenkephalin, the biosynthesis of 5 additional Met5-enkephalin-containing peptides was also examined. We determined that the posttranslational processing of proenkephalin did not yield exclusively penta-, hepta-, and octapeptides but larger opioid peptides as well in both control and lesioned animals, and that the ratio of the enkephalin peptides was not altered following the lesion. Measurement of preproenkephalin messenger RNA levels in the granule cells by Northern analysis revealed a marked increase following the lesion. Compared with the control animals, preproenkephalin mRNA was 8.5-fold higher in the contralateral dentate gyrus at 12 hr postlesion and 14- to 15-fold higher by 24 hr.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Enkephalin biosynthesis and enkephalin gene expression are increased in hippocampal mossy fibers following a unilateral lesion of the hilus. 355 11

Studies were undertaken to determine whether enhancement of GABAergic transmission within the substantia nigra could inhibit seizures caused by the novel, long latency convulsant, L-methionine, sulfoximine (MSO; 200 mg/kg i.p.). Bilateral injections of gamma-vinyl GABA (10 micrograms/side) into several brain sites resulted in varying degrees of protection against MSO-induced seizures. However, significant protection was afforded only when gamma-vinyl GABA was infused into the nigra. The protective effect was reduced when injections were made at sites 2 mm dorsal to the nigra, and was further diminished when the drug was injected into the striatum. These results further support the hypothesis that elevation of cerebral GABA levels is protective against a range of experimentally induced seizures, particularly when the substantia nigra is the target of such manipulations.
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PMID:Suppression of methionine sulfoximine seizures by intranigral gamma-vinyl GABA injection. 360 44

This chapter deals with the neurochemical consequences of the administration of the chemical convulsant agent L-methionine-dl-sulfoximine (MSO) on the brain of rodents. The principal notion is that this convulsant agent differs qualitatively from most quick-acting and predominantly lethal convulsant agents, commonly used in laboratory studies in epilepsy modeling because it has a preconvulsant latency period of several hours and also because it need not be fatal to the animals receiving it if they are properly managed during the preconvulsant period and following the first seizure attack. The historical profile of MSO as a useful and unique laboratory tool for neurochemical and molecular studies is briefly recounted, and the point is made that MSO is a close derivative of the amino acid L-methionine, which is used by each and every brain cell as a protein building block and as a precursor of the universal cellular methyl donor molecule, S-adenosyl-L-methionine. The importance of methylations, a set of reactions which consist in the transfer of the methyl group of S-adenosyl-L-methionine to several dozens of endogenous methyl acceptor molecules, small and large, is stressed and reviewed both historically and as this process relates to MSO epileptogenesis. The multiple effects of MSO on the methylation of small MW compounds, histamine being the working example, are reviewed. The involvement of phospholipid, nucleic acid, and protein methylations, all apparent targets of MSO action, in that they respond to the MSO challenge by a significant rate increase is elucidated. Finally, the effects of MSO at the functional level of brain receptor action are presented.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cerebral methylations in epileptogenesis. 370 18

Blood-brain barrier (BBB) permeability to macromolecules was assessed during seizures induced by pentylenetetrazole, bicuculline, methoxypyridoxine, methionine sulfoximine, and kainic acid. It was observed that each convulsant induced a specific pattern of regional BBB opening. This was, however, only the case when systemic blood pressure (BP) rose with seizure onset. The analysis of regional cerebral blood flow revealed that a high increase in flow in rabbits with BP rise is related to the normal flow at rest in the single brain region, but not to BBB permeability. In rabbits without BP increase, regional flow increase was low but well modulated and is possibly a better indicator for neuronal activity. The ultrastructural analysis showed that macromolecular transport over the cerebrovascular endothelium is by pinocytosis, an neurotransmitter controlled process. It is suggested that seizure-induced regional BBB opening is determined by two factors: release of neurotransmitters due to the process of auto-regulation during peripheral pressure increase, and change in local neurotransmitter milieu due to the action of the convulsant and/or the seizure activity.
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PMID:Pathophysiological aspects of blood-brain barrier permeability in epileptic seizures. 378 3

Structural analogues of the potent known anticonvulsant agent N-acetyl-DL-alanine N-benzylamide (1a) have been prepared (16 examples). The pharmacological activities of these products were evaluated in the maximal electroshock seizure (MES), the subcutaneous pentylenetetrazole seizure threshold (sc Met), and the rotorod (Tox) tests. The median effective doses (ED50) and the median toxic doses (TD50) for the most active compounds by both intraperitoneal and oral administration are reported. The most active compounds were N-acetyl-DL-phenylglycine N-benzylamide (1d) and N-acetyl-DL-alanine N-m-fluorobenzylamide (1m) along with the parent compound 1a. The ED50 values in the MES test for these three compounds compared well with phenobarbital, while their high TD50 values contributed to their large protective indexes, which approached that of phenytoin. When tested against four convulsant agents, compounds 1a and 1d displayed activity profiles significantly different from those reported for conventionally used antiepileptic drugs.
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PMID:Functionalized DL-amino acid derivatives. Potent new agents for the treatment of epilepsy. 382 Feb 28


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