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

The effect of pentobarbital and phenytoin on the high-affinity uptake of the putative neurotransmitters gamma-aminobutyric acid (GABA), glutamate, and norepinephrine was examined in synaptosomes prepared from rat brain. Both pentobarbital and phenytoin inhibited the uptake of norepinephrine. Pentobarbital increased the uptake of GABA twofold and only slightly increased the uptake of glutamate. Phenytoin facilitated GABA uptake to a lesser extent than did pentobarbital, but also increased the uptake of glutamate. This suggests that these drugs may limit the propagation of seizures through the balance of excitatory glutamate pathways and inhibitory GABA and norepinephrine pathways. The contrasting effects of these drugs on GABA and glutamate uptake may be related to the hypnotic properties of pentobarbital not present in phenytoin.
 ...
PMID:Mechanism of action of anticonvulsants. Role of the differential effects on the active uptake of putative neurotransmitters. 0 91

Veratridine causes deplorization of excitable cells and produces marked elevation of adenosine 3',5'-monophosphate (cyclic AMP) and guanosine 3',5'-monophosphate (cyclic GMP) levels in incubated slices of mouse cerebral cortex. Phenytoin, carbamazepine, phenobarbital, primidone, phensuximide, methsuximide, alpha-methyl-alpha-phenylsuccinimide, and high concentrations of clonazepam are anticonvulsant drugs that preferentially prevent maximal electroshock seizures (MES) and generalized tonic-clonic convulsions; all these agents inhibit veratridine-induced accumulation of both cyclic AMP and cyclic GMP. In contrast, ethosuximide, trimethadione, valproic acid, and low concentrations of clonazepam are anticonvulsant drugs that act predominantly against Metrazol and absence seizures; these agents are ineffective or inhibit accumulation of only cyclic GMP. The results suggest that inhibition of cyclic AMP and cyclic GMP accumulation in depolarized brain tissue is a molecular neuropharmacological action characteristic of anticonvulsant drugs that have direct effects on cellular membrane function and prevent MES. Anticonvulsant drugs that do not inhibit accumulation of both cyclic AMP and cyclic GMP in depolarized brain tissue preferentially prevent Metrazol and absence seizures and probably exert their effects by altering neurotransmission mechanisms.
 ...
PMID:Inhibitory effects of anticonvulsant drugs on cyclic nucleotide accumulation in brain. 3 36

Several interactions involving antiepileptic drugs are based on changes in the rate of their metabolism and elimination, with concomitant rise or fall of plasma levels. Thus, phenobarbital generally induces the production of the DPH metabolizing enzyme, but its presence inhibits the action of that enzyme. The net result depends upon the balance between these factors in individual patients. Either a decline, a rise, or no change of the DPH plasma level may occur after the onset of administration of phenobarbital. Drugs that may cause elevation of the DPH plasma level include disulfiram, sulthiame, bishydroxycoumarin, chloramphenicol, phenyramidol, benzodiazepines, sulfamethizole, and isoniazid. Isoniazid has been shown experimentally to be a strong inhibitor of DPH metabolism. The extent of DPH plasma level elevation by INH is related to the genetic make-up of individual patients. The highest and frequently toxic DPH plasma levels were seen in very slow INH inactivators. The incidence of clinically significant interactions is not high with most drug combinations; marked changes of antiepileptic drug levels occur only in apparently susceptible individuals. The effects of interactions are not necessarily detrimental; elevation of a low ineffective level may improve seizure control. A rise to a toxic level range requires reduction of the dose of primary drug or elimination of interfering drugs. Monitoring the blood levels of anti-epileptic drugs provides the best means to anticipate interactions and to regulate the doses when multiple medications have to be used.
 ...
PMID:Interactions of antiepileptic drugs. 5 Feb 32

Convulsive activity was induced in functionally decapitate cat preparations by topical and by systemic administration of toxic amounts of penicillin. The paroxysmal movement patterns and the electrographic signs of spinal seizure activity recorded from spinal ventral and dorsal roots and from the dorsal surface of the spinal cord are described. Paroxysms of interictal myoclonic twitching as well as tonic and clonic ictal seizures reminiscent of epileptiform convulsions of intact animals were seen in the absence of descending influences from the brain. Tonic seizures consisted of flexion--extension sequences; co-contraction of antagonistic muscles was the rule. Clonic activity consisted of rhythmic discharges at 4--6/sec, In dorsal roots, electrotonically conducted paroxysmal negative potential shifts as well as antidromically conducted trains of impulses were recorded. Ictal paroxysmal waves of the cord dorsum potential consisted of either biphasic positive--negative sequences or of purely negative waves. Diphenylhydantoin effectively controlled spinal seizures in the absence of a functioning cerebellum. Diphenylthiohydantoin changed the pattern of seizures, suppressing all ictal activity and greatly enhancing the amplitude and frequency of interictal bursts. Three different barbiturates suppressed seizure activity, but diazepam was ineffective, indicating that the site of its clinical anticonvulsant action may be supraspinal. Seizure activity, once induced, continued for up to 18 h. Intravenous administration of penicillinase abolished seizures indicating that their usual persistence is caused by the presence of the drug in the tissue, not by an irreversible biochemical lesion.
 ...
PMID:Motor and electrical signs of epileptiform activity induced by penicillin in the spinal cords of decapitate cats. 6 Feb 12

Twenty chronic epileptics receiving phenytoin and either phenobarbitone or primidone have been studied. All patients had frequent seizures and had serum concentrations of phenytoin below 410 mumol/1. Phenytoin dosage was increased to study the effect on the frequency of seizures and the serum concentrations of phenytoin and phenobarbitone. There was no effect on minor seizures but in ten out of sixteen patients major seizures were abolished or reduced. Serum concentrations of phenobarbitone rose as the phenytoin dose was increased. This may cause deviations from the expected relationship between dose and serum concentrations of phenytoin; this would explain deficiencies which were found in a nomogram for predicting the therapeutic dose of phenytoin.
 ...
PMID:Therapeutic and pharmacokinetic effects of increasing phenytoin in chronic epileptics on multiple drug therapy. 7 51

Left-sided motor seizures in a patient with an operated brain tumor were controlled with 300 mg/d DPH. The introduction of antimicrobial therapy with nitrofurantoin caused a fall of serum DPH levels and the recurrence of seizures, at the same time serum gammaGT values were increased. These changes were reversible after nitrofurantoin treatment was terminated. Both increased DPH metabolism or impaired absorption could be responsible for this effect. The concomittant increase of gammaGT could be interpreted as indirect evidence of hepatic enzyme induction with increased metabolism of DPH. It is important to note the possibility of such interaction so that better anticonvulsant control can be achieved.
 ...
PMID:Interaction of nitrofurantoin with diphenylhydantoin. 8 Dec 79

Serotonin was determined in platelets of 140 patients with idiopathic mal seizures. According to anticonvulsive therapy these patients were divided into the following five groups: no medication, Diphenylhydantoin, Diphenylhydantoin calcium, Primidon, and combination of various of the anticonvulsants mentioned. The results obtained in the entire group of patients as well as in the various subgroups were compared with those of a group of healthy persons without therapy. In addition the various subgroups were compared to each other. There were significantly reduced serotonin values in the patients with idiopathic grand mal seizures as well as in each of its various groups as compared with the values obtained in healthy persons. Furthermore, significantly higher values were observed in the patients receiving primidone as compared with those receiving no anticonvulsants, Diphenylhydantoin, and a combination of various anticonvulsants. Our results taken together with those reported in the literature point to the possibility that a special imbalance in the cerebral neurotransmitter system, including a deficiency of serotonin, may represent a pathogenetic factor for idiopathic grand mal seizures. In addition, this investigation indicates that primidone elevates serotonin in platelets of patients with grand mal seizures.
 ...
PMID:Serotonin metabolism with idiopathic grand mal seizures. 8 62

An elderly man had focal motor status epilepticus secondary to a frontal lobe hematoma. Phenytoin, phenobarbital, and diazepam did not stop the seizures. Intravenous lidocaine by bolus injection and continuous infusion rapidly controlled the seizures.
 ...
PMID:Lidocaine: a neglected anticonvulsant? 11 54

Drug treatment of status epilepticus is reviewed. Tonic-clonic, focal motor, complex partial and absence status epilepticus are discussed. In managing tonic-clonic status epilepticus one should: (1) maintain vital functions at all times, (2) identify and treat precipitating factors and (3) administer an intravenous loading dose of phenytoin sodium or phenobarbital sodium. Careful use of i.v. diazepam sometimes helps to achieve these objectives. Intravenous phenytoin sodium and phenobarbital sodium provide definitive, long-term control of tonic-clonic seizures but must be administered slowly and require time to reach peak brain concentrations. Intravenous diazepam appears to enter and exit from the brain rapidly and may control seizures while therapeutic brain concentrations of long-acting drugs are being achieved. Phenytoin, phenobarbital and diazepam should not be administered intramuscularly in treating status epilepticus. Treatment of focal motor and complex partial status epilepticus is similar to that of tonic-clonic status epilepticus, but i.v. diazepam is required less frequently and loading doses of phenytoin and phenobarbital sometimes can be given more slowly. Status epilepticus of the absence type is managed with i.v. acetazolamide sodium or diazepam. Paraldehyde, muscle relaxants, general anesthesia and lidocaine may be tried when conventional therapies fail.
 ...
PMID:Drug therapy reviews: drug therapy of status epilepticus. 15 Feb 28

Post-tetanic potentiation (PTP) of monosynaptic reflex was estimated in spinal cords in the drug-free state after the administration of a convulsant dose of penicillin and after the administration of phenytoin. There was no apparent correlation between the degree of depression of PTP and the efficacy of controlling seizure activity by phenytoin. Extracellular potassium levels were measured with ion-selective microelectrodes. The post-stimulation clearing of [K+]0 was not accelerated by phenytoin, and frequently it was slowed. Post-stimulus undershooting of [K+]0 was diminished. Oxidation of NADH in cortex and of cytochrome a, a3 in spinal cord were measured by optical methods. Stimulus-evoked transient oxidation responses evoked by electrical stimulation were depressed by phenytoin. It is concluded that systemic administration of phenytoin in therapeutic doses does not stimulate Na+-K+-activated membrane ATPase in cortex and spinal cord. Unlike other depressants, phenytoin did not cause a reduction of "resting" redox levels of respiratory enzymes. The local regulation of blood flow remained unaltered after phenytoin administration. Phenytoin caused a moderate but consistent depression of the stimulus-evoked responses of potassium activity, electric potential, and oxidative enzymes, consistent with diminished outflow of potassium from cells, owing either to lesser activation of cells or to a lesser exchange of ions.
 ...
PMID:Phenytoin, electric, ionic, and metabolic responses in cortex and spinal cord. 19 41


1 2 3 4 5 6 7 8 9 10 Next >>