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)

Transplacental passage of cocaine in response to maternal administration of intravenous (IV) cocaine in doses of 1.0 and 2.0 mg/kg was studied in 6 pregnant ewes and fetuses and correlated with maximum changes in maternal and fetal blood pressures (BP), heart rates (HR) and fetal arterial blood gas values. Certain animals were given larger doses (3.0 and 5.0 mg/kg) of cocaine to examine cocaine-related cardiopulmonary and neurologic sequelae. Cocaine was extracted on C-18 sorbent columns and analyzed by gas chromatography. At 1.0 and 2.0 mg/kg, cocaine produced dose-dependent increases in maternal HR and BP which were maximum by 1 minute. The fetal response was characterized by maximum increases in BP and decreases in PO2 by 3 minutes and increases in HR by 15 minutes. Cocaine rapidly appeared in the fetal circulation, was approximately 15% of maternal concentrations by 5 minutes, and was undetectable in both circulations by 60 minutes. At cocaine doses of 3.0 and 5.0 mg/kg significant maternal cardiopulmonary and neurologic complications were encountered including bradyarrhythmias, respiratory distress, seizure and death. These data indicate that cocaine exerts direct drug actions upon maternal cardiovascular and neurologic function. In addition, cocaine affects fetal cardiovascular function directly via transplacental passage and indirectly by fetal hypoxemia from cocaine-induced uterine artery vasoconstriction. (NIDA 04415)
 ...
PMID:Prenatal cocaine exposure to the fetus: a sheep model for cardiovascular evaluation. 250 Aug 83

Graded seizure responses to suprathreshold cerebral electroshock in mice were modified by drugs acting at mu- and at delta-opioid receptors. Morphine exerts a proconvulsant effect at a non-mu opioid receptor and may exert a simultaneous anticonvulsant effect at a mu-opioid receptor. Delta-opioid receptor blockade increases seizure severity, suggesting a predominantly anticonvulsant nature of the delta-opioid system in the seizure model tested here.
NIDA Res Monogr 1986
PMID:Mu- and delta-opioid modulation of electrically-induced epileptic seizures in mice. 282

Enantiomers of delta-6-tetrahydrocannabinol (THC), delta-6-THC-1'', 1''-dimethylheptyl (DMHP), and 7-OH-delta-6-THC-1'',1''-DMHP were assessed for their ability to block audiogenic seizures in genetically epilepsy-prone rats. The stereoisomers were evaluated also for their ability to produce differential neurotoxicity in the rat rotorod (ROT) paradigm. Potency comparisons among the compounds revealed modest to profound stereoselectivity for anticonvulsant and neurotoxic activities, a general increase in both activities with the DMHP and 7-OH modifications of delta-6-THC, and some favorable separation between anticonvulsant and neurotoxic activities with selected THC analogs.
NIDA Res Monogr 1987
PMID:Anticonvulsant and neurotoxic effects of tetrahydrocannabinol stereoisomers. 283 May 38

Dynorphin A (1-13) acutely elevated the seizure threshold (ST) to the convulsant flurothyl, and this action was not blocked by naloxone. Increases in ST were also observed following i.c.v. injections of the non-opioid fragment dynorphin A (3-13). Pretreatment with dynorphin A (1-13), but not dynorphin A (3-13), non-competitively blocked the anticonvulsant effect of the mu selective opioid DAGO. Furthermore, pretreatment with dynorphin A (1-13) antagonized the delta antagonist properties of naloxone or ICI 154,129 in this seizure model. Thus, in addition to its non-opioid anticonvulsant effects, dynorphin A (1-13) exhibits unique antagonist actions which appear to be specific for the active opioid fragment.
NIDA Res Monogr 1986
PMID:Dynorphin A (1-13): in vivo opioid antagonist actions and non-opioid anticonvulsant effects in the rat flurothyl test. 289 82

The evidence accumulated so far indicates that seizure activity exerts profound changes on the metabolism of opioid peptides in the hippocampus. Our data consistently show a large transient decrease in dynorphin and a modest decrease in enkephalin in the hippocampus following either a single ECS or KA injection. These initial reductions, which are indicative of increased release, may trigger the biosynthetic process of hippocampal opioids and result in an overproduction of the peptides seen in the rebound phase. However, the amount and timing of the rebound in enkephalin and dynorphin levels in response to repeated ECS, amygdaloid kindling, or KA differ drastically: a rapid and sustained increase in ME-LI follows all three treatments, in contrast to a slow recovery after a large and sustained decrease in DN-LI induced by repeated ECS and amygdaloid kindling. These results, which are unique to the hippocampus, suggest that differential mechanisms are operative in regulating the metabolism of these two opioid peptides in the hippocampus. It is likely that a well-coordinated regulation of hippocampal function can be achieved through the differential release of enkephalin and dynorphin and their subsequent interactions at different subtypes of opioid receptors following seizure activities. From a functional point of view, our data provide a neurochemical correlate of previous reports that brain opioid peptides may mediate ECS-induced behavioral alterations, such as changes in seizure threshold, postictal depression, and retrograde amnesia. The robust changes in the levels of opioid peptides in kindled rats, plus shortening of the kindling process by pretreatment with mu opioid antagonists, strongly suggest the involvement of brain opioid peptides in the development of kindling. Finally, these studies show clear evidence that enkephalin in the hippocampus is important in KA-induced WDS, a component of the opiate withdrawal syndrome in rodents (Isaacson and Lanthorn 1981). Further studies should help distinguish the regulatory mechanisms responsible for changes in opioid peptide metabolism during states of hyperexcitability in the hippocampal formation.
NIDA Res Monogr 1988
PMID:Seizure-induced alterations in the metabolism of hippocampal opioid peptides suggest opioid modulation of seizure-related behaviors. 289 42

Until now, we have measured dynorphin-ir and enkephalin-ir at only a few time points after a single seizure or after multiple seizures in most of the models we have employed. Except for the genetically seizure-prone gerbil, our data consistently show a transient and robust decrease in dynorphin-ir and a sustained increase in enkephalin-ir in the hippocampal formation subsequent to kainic acid-, ECS-, or amygdaloid-kindled convulsive seizures. At this point, kainic acid appears to have the most dramatic effects on hippocampal enkephalin and dynorphin levels, causing an initial decrease followed by a rebound increase beyond control levels, which, for met5-enkephalin, is maintained for at least 2 weeks. Recurrent seizures leading to neurotoxic effects on CA3 pyramidal cells, which are not present after ECS or kindling, may underlie the sustained alteration in enkephalin metabolism after kainic acid. Further investigation into the time course of seizure-induced enkephalin and dynorphin metabolic changes using RIA, ICC, and measurements of opioid mRNA levels may reveal a common pattern of depletion due to immediate release, rebound synthesis according to the severity of demand, and stabilization at a new equilibrium over several days or even weeks in each seizure model. Our preliminary time points suggest striking differences in the rate of metabolism of hippocampal dynorphin and enkephalin in response to seizures. We would like to find out if other perturbations of the hippocampus, primarily the elimination of the influence of its known neurochemical afferents by lesion (as performed on the septohippocampal system described above) or pharmacological blockade, can alter the metabolism of hippocampal opioid peptides and influence subsequent seizure transmission. Distinguishing the physiological conditions that induce metabolic changes in discrete opioid peptidergic pathways may help us to understand how endogenous opioids are involved in the regulation of neuronal excitability in specific brain regions, as well as to understand more about the differential regulation of opioid peptide metabolism in different brain pathways.
NIDA Res Monogr 1986
PMID:Modulation of opioid peptide metabolism by seizures: differentiation of opioid subclasses. 302 38

Bilateral, recurrent seizures were induced in adult male rats by a unilateral, electrolytic lesion of the dentate gyrus hilus. This treatment led to a bilateral depletion of enkephalin-like immunoreactivity in the hippocampal mossy fibers by 12 hours (h) post-lesion, a rebound above normal levels by 24 h, a further rise by 4 days than a fall to control values by 10 days post-lesion. The mRNA for preproenkephalin was elevated in the granule cells by 3h post-lesion, reached a maximal 24-fold rise by 30 h then fell again to control values by 4-10 days post-lesion.
NIDA Res Monogr 1986
PMID:Increased enkephalin gene expression in the hippocampus following seizures. 312 57

Increasing doses of naloxone hydrochloride (100-1000 nmol) were micro-injected unilaterally into the rat amygdala and the behavioral, neuropathological and electrographic responses were studied. Microinjections of low doses of naloxone (100-250 nmol) produced staring, gustatory automatisms and wet shakes whereas higher doses additionally resulted in motor limbic seizures and status epilepticus. The electroencephalogram showed a sequence of alterations characterised by high voltage fast activity, spiking, bursts of polyspiking, electrographic seizures and postictal depression which first appeared in the amygdala and rapidly spread to hippocampal and cortical areas. The neuropathological analysis of frontal forebrain sections by means of light microscopy revealed seizure-related brain damage in amygdala, olfactory cortex, thalamus, hippocampal formation, substantia nigra and neocortex. Diazepam, 10 mg/kg i.p., when given prior to the microinjection of naloxone into the amygdala, abolished the epileptogenic and neurotoxic effects of the drug. The results suggest that naloxone, when microinjected into rat amygdala elicits electrographic and motor limbic seizures followed by seizure-related brain damage.
NIDA Res Monogr 1986
PMID:Convulsant action of naloxone in the rat amygdala. 312 74

Microinjection of morphine hydrochloride into the substantia nigra pars reticulata, bilaterally, converts non-convulsant dose of pilocarpine hydrochloride, 100 mg/kg, into a convulsant one. The ED50 of morphine for the generation of seizures after pilocarpine, 100 mg/kg, is 3.8 nmol (2.5-5.8). Electrographic and behavioral monitoring both show a pattern of convulsant activity similar to those produced by pilocarpine in doses exceeding 350 mg/kg. Morphological analysis of frontal forebrain sections reveals epilepsy-related damage to the hippocampus, thalamus, olfactory cortex, substantia nigra, neocortex and amygdala. The proconvulsant action of morphine in the substantia nigra is reversed by co-administration of naloxone hydrochloride. The results show that the threshold for limbic seizures may be modulated by opiates in the substantia nigra.
NIDA Res Monogr 1986
PMID:The threshold for limbic seizures in rats is decreased by intranigral morphine. 312 75

Cannabidiol (CBD) exhibits anticonvulsant activity in experimental animals and in man. As part of a structure-activity study, analogs were prepared wherein the terpene unit, the aryl unit, and/or the side chain were modified. Thus, several pinenyl and carenyl derivatives, aryl ethers and acetates, and a variety of 1",1"-dialkylhexyl and 1",1"-dialkylheptyl analogs were synthesized. The compounds were evaluated for anti-convulsant activity in seizure susceptible (AGS) rats and for neurotoxicity in the rat rotorod (ROT) test. Comparisons of stereoisomers of CBD and several analogs revealed a general lack of stereoselectivity for anticonvulsant and other CNS properties of this class of compounds.
NIDA Res Monogr 1987
PMID:Structure-anticonvulsant activity relationships of cannabidiol analogs. 312 80


1 2 3 Next >>