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

In mice, the influence of small (analgesic range) doses of morphine, fentanyl, meperidine and pentazocine on the thresholds for seizures induced by electroshock and pentetrazole was studied. The antinociceptive ED50 was determined against writhing induced by acetic acid or morphine (0.43 mg/kg, s.c.), fentanyl (0.018 mg/kg, s.c.), meperidine (2.6 mg/kg, s.c.), and pentazocine (2.0 mg/kg, s.c.). The electroconvulsive threshold was significantly elevated at doses slightly greater than (fentanyl and meperidine) or about twice the antinociceptive ED50 (morphine and pentazocine). Naloxone antagonized this effect in the case of morphine and fentanyl, but not in the case of meperidine and pentazocine. The threshold for clonic convulsions induced by intravenous infusion of pentetrazole was not influenced by morphine, fentanyl and meperidine, in the dose range studied, but was slightly increased by the smaller doses (2 and 4 mg/kg) of pentazocine. The tonic phase of pentetrazole-induced convulsions was suppressed by the larger doses of fentanyl, meperidine and pentazocine, though smaller doses of pentazocine significantly reduced the threshold for the extensor phase.
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PMID:Effect of morphine and morphine-like analgesics on susceptibility to seizures in mice. 287 17

There are four lines of evidence for or against a role of neuropeptides in epilepsy: Administration of a variety of opiate agonists into the ventricles or brain of animals produces a constellation of electrical and behavioral changes, seemingly receptor-specific, both sensitive to the specific opiate antagonist naloxone as well as certain anticonvulsant drugs. The primary reservation concerning these data in terms of their relevance to epilepsy regards the fact that the peptides are exogenously administered in relatively high doses. Hence, these data may reflect neurotoxic effects of peptides rather than physiologic function. A variety of opiate agonists are anticonvulsant and naloxone shortens the postictal state in some experimental seizure models. One could attempt to reconcile these data with those in No. 1 by hypothesizing that the spikes and behavioral changes examined in the latter experimental parodynes represented a sort of isolated model of the postictal state. Naloxone has little effect in clinical epilepsy. These data are far from conclusive for two reasons. First, few patients have been studied. Second, because of the issue of opiate receptor heterogeneity and the high doses of naloxone needed experimentally to block non-mu opiate effects, the doses of naloxone used clinically to date are too low to rule out possible delta- or epsilon-mediated effects. The negative clinical data are illustrative of the dangers and difficulties of extrapolating data generated in animal models of seizures to the human condition. ACTH, a peptide that is derived from the same precursor molecule as beta-endorphin, is clearly an effective anticonvulsant in certain childhood seizure states. However, whether this is due to a direct or indirect (that is, cortisol) effect on brain is far from clear. Paradoxically, in contradistinction to other data concerning pro- and anticonvulsant properties of various opioid peptides, there is no animal model of infantile spasms to help resolve this important question.
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PMID:Neuropeptides and seizures. 302 83

Repeated spaced injection of small amounts of beta-endorphin or Met-enkephalin into the hippocampus or posterior amygdala of the rat led to the development of kindled generalized convulsions. Similar injection of morphine into the hippocampus or anterior amygdala resulted in epileptiform spiking followed by tolerance. The epileptiform spiking and convulsive behavior varied in a dose-related manner. Naloxone blocked or greatly attenuated the electrographic seizure and convulsive behavior. Prior kindling with beta-endorphin or Met-enkephalin significantly facilitated electrical kindling of the amygdala. Handling or conspecific threat potentiated the epileptiform spiking and convulsive behavior in some cases. The results indicate that the epileptogenic response to intracerebrally applied opioid peptides is site-specific within the rat brain, and they support the idea that endogenous opioid mechanisms may play a role in convulsive seizures. They also suggest a possible opiate-based mechanism for the stress-induced exacerbation of seizures.
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PMID:Epileptiform effects of met-enkephalin, beta-endorphin and morphine: kindling of generalized seizures and potentiation of epileptiform effects by handling. 316 84

The influence of intraperitoneal delta-sleep inducing peptide (DSIP) injection (100 micrograms/kg) on the epileptic activity was investigated in the experiments on Wistar rats and (CBA X C57B1/6)F1 mice. The model of chronically developing epileptic activity--the model of pharmacological kindling--was created by daily repeated corasole injections in subconvulsive doses (30 mg/kg). It has been shown that DSIP injection delayed the manifestation of generalized seizures during kindling, led to the suppression of seizure activity and reduced the mortality rate of animals that developed kindled seizures. The antiepileptic effect of DSIP was observed throughout the period of 5 minutes to 24 hours after the injection. Naloxone (2.5 mg/kg) did not change the antiepileptic effect of DSIP.
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PMID:[The effect of delta sleep-inducing peptide on the convulsive activity in corasol kindling]. 316 73

In a previous study we found depressed ACTH and normal beta-endorphin values in the cerebrospinal fluid of patients with West's syndrome, whereas normal peptide levels were present in infants with secondary Infantile spasms. This prompted us to study the effects of naloxone administration in children with West's syndrome. After informed consent was obtained from the parents, the effects of naloxone administration on clinical and EEG findings were evaluated in five infants 5-9 months old (3 males, 2 females) with cryptogenic infantile spasms and hypsarrhythmia. The infants were studied at the onset of symptomatology before therapy. An average of 5-10 groups of spasms were present per day. Naloxone (12 micrograms/kg body weight) was administered as an intravenous bolus in two cases, as a slow venous drip in another two cases, and intramuscularly in the last case. EEG and polygraphic monitoring were performed for 2 h. Naloxone did not induce any acute behavioral changes and the number of seizures remained unchanged after treatment. These data reject the possibility that endogenous opioids tonically modulate infantile spasms. Further studies are required to ascertain the involvement of POMC peptides in West's syndrome.
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PMID:Lack of clinical-EEG effects of naloxone injection on infantile spasms. 324 47

'Designer drugs' are substances intended for recreational use which are derivatives of approved drugs so as to circumvent existing legal restrictions. The term as popularised by the lay press lacks precision. Contrary to the popular belief that 'designer drugs' are original creations, the majority of these agents are 'borrowed' from legitimate pharmaceutical research. They merely represent the most recent developments in the evolution of mind-altering chemicals. The most extensively studied class of psychoactive compounds is the phenylethylamines (mescaline analogues). This class includes catecholamines, therapeutic agents and numerous illicit derivatives. Subtle alterations of the phenylethylamine molecule give rise to a spectrum of pharmacological properties ranging from pure sympathomimetic stimulation to primarily psychoactive effects. Although most of these compounds are only of historical interest, amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), and 3,4-methylenedioxymethamphetamine (MDMA) continue to be used recreationally. Many deaths have been ascribed to this class of compounds. In overdose the differences between these compounds blur and the clinical presentation is similar to that of amphetamine overdose characterised by tachycardia, hypertension, hyperthermia, diaphoresis, mydriasis, agitation, muscle rigidity, and hyper-reflexia. Death usually results from arrhythmias, hyperthermia or intracerebral haemorrhage. Treatment is aggressive and supportive with careful attention to temperature, blood pressure and seizure control. Synthetic opioid derivatives, which represent the second major class of 'designer drugs', are derivatives of fentanyl (e.g. alpha-methylfentanyl, 3-methylfentanyl) or pethidine (meperidine) and are extremely potent compounds responsible for numerous overdose deaths. Attempts to synthesise pethidine have resulted in the accidental production of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), a compound which is metabolised in the brain by the monoamine oxidase system to a toxic intermediate (MPP+) which selectively destroys the sustantia nigra, resulting in the rapid onset of severe Parkinsonian symptoms. Naloxone will antagonise the opiate effects of this drug class, although high doses may be required. Arylhexylamines constitute the third class of 'designer drugs'. The predominant member of this class is phencyclidine (PCP), a derivative of the anaesthetic ketamine. This unique class of psychoactive agents exhibits broad and complex pharmacological effects.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:'Designer drugs'. A problem in clinical toxicology. 328 24

Morphine hydrochloride (25-200 nmol), [D-Ala2, D-Leu5]enkephalin (10-200 nmol) and naloxone hydrochloride (100-1000 nmol) were injected unilaterally into the rat amygdala and the following electrographic, behavioural and neuropathological responses were studied. Microinjections of low doses of morphine (25-50 nmol) resulted in behavioural alterations characterized by staring, gustatory automatisms and wet shakes, whereas higher doses additionally produced motor limbic seizures and status epilepticus. The first changes in the electroencephalogram appeared in the amygdala immediately after the administration of morphine and rapidly spread to hippocampal and cortical areas. Electrographic alterations consisted of high voltage fast activity, spiking, bursts of polyspiking, electrographic seizures and periods of postictal depression. Neuropathological analysis of frontal forebrain sections by means of light microscopy revealed widespread, seizure-related damage confined to amygdala, olfactory cortex, thalamus, hippocampal formation, neocortex and substantia nigra. Pretreatment of animals with naloxone, 2-20 mg/kg s.c., as well as simultaneous microinjection of the non-convulsant dose of naloxone, 100 nmol, with morphine, 100 nmol, into the amygdala failed to block the development of convulsant activity and seizure-related brain damage produced by the opiate. In contrast, diazepam, 10 mg/kg i.p., when administered prior to the microinjection of morphine into the amygdala, abolished the epileptogenic effects of the drug. [D-Ala2, D-Leu5]Enkephalin, 10-200 nmol, elicited electrographic and behavioural responses similar to those seen after low doses of morphine, when administered into the amygdala. High voltage fast activity, single spikes, bursts of polyspiking, electrographic seizures and periods of postictal depression were seen in the electroencephalogram, but no behavioural signs of motor limbic seizures could be detected. The only behavioural correlates of epileptiform electrographic activity were wet shakes, myoclonic head twiches and gustatory automatisms. The examination of frontal forebrain sections from rats receiving [D-Ala2, D-Leu5]enkephalin revealed no morphological changes. Pretreatment of rats with either naloxone, 2 mg/kg, or diazepam, 10 mg/kg, blocked the development of behavioural and electrographic sequelae of the peptide. Naloxone, 100-1000 nmol, when microinjected into the amygdala, produced electrographic, behavioural and morphological alterations resembling those seen after high doses of morphine.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Convulsant action of morphine, [D-Ala2, D-Leu5]-enkephalin and naloxone in the rat amygdala: electroencephalographic, morphological and behavioural sequelae. 329 87

Interictal changes in locomotor and shock-response behaviors were examined in rats that were kindled unilaterally or bilaterally in the amygdala. 2-Deoxyglucose and naloxone were used to test whether alterations in cerebral glucose metabolism or opioid functioning, respectively, correlated with changes in these behaviors. Bilaterally kindled rats, at 14 to 28 days after their last seizure, displayed increased locomotion (square crossing) in an open field compared with unilaterally kindled or control rats. Bilaterally kindled rats also showed elevated thresholds for the elicitation of a multiple squeak response to tail shocks. Single squeak or tail withdrawal responses to tail shock were not affected by bilateral kindling. Likewise, unilaterally kindled rats did not differ from controls on any of the behavioral measures. Naloxone (10 mg/kg, i.p.) reversed the increase in locomotion and elevation of multiple squeak thresholds in the bilaterally kindled rats. By itself, naloxone did not influence any of the behaviors. Finally, cerebral glucose metabolism was decreased, globally, in the forebrain of the bilaterally kindled rats, and naloxone normalized this change. Cerebral metabolism was not altered in unilaterally kindled rats compared with controls. Thus, changes in cerebral metabolism and opioid functioning may be involved in the mediation of interictal changes in locomotor and emotional behavior in rats.
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PMID:Interictal changes in behavior and cerebral metabolism in the rat: opioid involvement. 333 45

The s.c. administration of morphine (2.5-80 mg/kg) produced a dose-dependent hyperglycemia, whereas morphine (12.5-50 micrograms) given i.t. in the lumbar region caused a dose-dependent hypoglycemia in unanesthetized mice. Both effects on blood glucose were antagonized by s.c. naloxone, although inhibition of i.t. morphine required a higher naloxone dose. Naloxone pretreatment with 2 mg/kg, but not 1 mg/kg s.c., potentiated a hyperglycemic response to i.t. saline. High i.t. doses of morphine caused an early (within 2 min) scratching behavior that was not inhibited by naloxone or glucose loading and a later (greater than 20 min) tonic convulsive behavior (opisthotonus). Lethality was partially inhibited by glucose loading which delayed, but did not prevent, the hypoglycemic effect of i.t. morphine. The hypoglycemic effect of i.t. morphine was also delayed in streptozotocin-diabetic ICR mice and diabetic (db/db) C57BL/KsJ mice, but the latter were more sensitive to lethality, which occurred without hypoglycemia or seizures. All these effects of i.t. morphine were completely blocked by acute spinal transection of T10-T11, but the nociceptive, hypoglycemic and opisthotonic effects were not mimicked by i.c.v. morphine (6.25-50 micrograms) in ICR mice, which showed a bell-shaped hyperglycemic dose-response relationship and a brief explosive motor behavior at the higher doses (25-50 micrograms). It is concluded that the effects of morphine on blood glucose and on behavior are dependent upon the route of administration, and that the convulsive effect of i.t. morphine may be facilitated by the production of a profound hypoglycemia, which involves a spinal, rather than supraspinal or systemic, action of morphine.
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PMID:Differential effects of subcutaneous and intrathecal morphine administration on blood glucose in mice: comparison with intracerebroventricular administration. 336 41

Scopolamine and naloxone were administered singly and in combination to different groups of rats undergoing electrical kindling of the amygdala. Scopolamine significantly reduced the maximal seizure stage attained during 15 drug sessions and increased the total number of afterdischarges required to kindle a generalized convulsion. Naloxone had a similar but weaker and nonsignificant effect. The results confirm that antagonism of muscarinic receptors by scopolamine retards amygdala kindling.
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PMID:Effects of treatment with scopolamine and naloxone, singly and in combination, on amygdala kindling. 355 20


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