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)

Previous work has demonstrated that thyrotropin-releasing hormone (TRH) and its beta-alanine analogue (beta-ala TRH) are potent antagonists of barbiturate-induced sedation. This study sought to determine the effects of these oligopeptides on the anticonvulsant properties of phenobarbital in the maximal electroshock seizure (MES) test. Pro-leu-gly-NH2, another hypothalmic peptide was also examined. None of the peptides studied had any anticonvulsant properties of their own, but TRH and beta-ala TRH, though not pro-leu-gly-NH2, potentiated the anticonvulsant potency of phenobarbital. Thyrotropin (TSH) and tri-iodothyronine (T3) were in effective, suggesting that the effects observed with TRH are not mediated via the pituitary-thyroid axis. Since phenobarbital treatment of grand mal epilepsy is often limited by sedation and since TRH antogonizes sedation and enhances anticonvulsant effects of the barbiturate, the hormone or a congener may find value as an adjunct in therapy.
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PMID:Thyrotropin-releasing hormone (TRH) and its beta-alanine analogue: potentiation of the anticonvulsant potency of phenobarbital in mice. 81 74

A 41-year-old woman is described, first hospitalized in the neurosurgical department for a transient ischemic attack with left hemiparesis followed after 6 hours by tonic-clonic seizures starting from the left hemiface and quickly generalized. Brain computed tomography (CT) scan and magnetic resonance imaging were normal. Clinically the patient presented tremor, tachycardia, generalized muscle weakness, and profuse diaphoresis. T4 and T3 were elevated. The patient was transferred from the neurosurgical to the medical department where a thyroid storm due to autoimmune Graves' disease with normal thyrotropin (TSH) values responsive to thyrotropin-releasing hormone (TRH) stimulation was diagnosed. A syndrome of inappropriate secretion of TSH was suspected in an unusual presentation as autoimmune Graves' hyperthyroidism. The TSH alpha-subunit and alpha-subunit/TSH molar ratio were normal, which supported the diagnosis of non-neoplastic inappropriate secretion of TSH. However, severe autoimmune Graves' hyperthyroidism is very rare indeed because autoantibodies to thyroid antigens are generally non-detectable in such patients. Our patient was treated initially with barbiturates, then with dexamethasone, Lugol's solution, methimazole and propranolol. Treatment of this patient proved difficult, and definitive improvement was obtained only after triiodothyroacetic acid administration, but methimazole and propranolol administration could not be discontinued. Fine needle aspiration biopsies of the thyroid in 2 occasions showed follicular or follicular-papillary proliferation with lymphocytic infiltration as in chronic thyroiditis. The patient is now in good clinical conditions and is followed up regularly. Autoimmune Graves' hyperthyroidism may be associated in extremely rare instances with non neoplastic inappropriate secretion of TSH.
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PMID:Thyroid storm with encephalopathic symptoms due to Graves' disease and inappropriate secretion of thyrotropin. 129 37

We have recently shown that seizures induce significant and sustained elevations of thyrotropin-releasing hormone (TRH) in specific extrahypothalamic rat brain regions associated with epileptic foci including amygdala, hippocampus, pyriform cortex, and anterior cortex. Seizures were induced in dogs to further study the effect on central nervous system TRH in a species known to show epileptiform seizures. Adult mongrel beagles were given pentylenetetrazol (PTZ) to induce generalized tonic-clonic seizures. Two groups of dogs were given either PTZ or saline every other day for four intravenous injections. Major motor seizures were observed visually and by electroencephalography with each PTZ injection, and these lasted from 3 to 10 minutes. Forty-eight hours after the fourth seizure, the dogs were killed and brains were removed, dissected, and stored at -90 degrees. After acetic acid extraction, extracts were assayed for TRH content by specific radioimmunoassay. Significant (P < 0.05) postictal TRH increases were seen in frontal cortex (1.5-fold), dorsal hippocampus (2.2-fold), pyriform cortex (2.5-fold), and amygdala (2.1-fold). Cerebellum, medulla, thalamus, hypothalamus, and septum showed no postictal changes in TRH. This report is the first to demonstrate TRH elevations in specific central nervous system regions associated with epileptic foci in the dog. Our results continue to stress the importance of the pyriform/periamygdaloid region as a key limbic region of endogenous TRH action in response to seizures and provides further evidence that TRH is either directly or indirectly involved in seizure modulation. Additional recent data from our laboratory and others suggest that this modulation is intrinsic to the hippocampus and may be anticonvulsant in nature.
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PMID:Regional changes in central nervous system thyrotropin-releasing hormone after pentylenetetrazol-induced seizures in dogs. 143 20

Examination of the neurobiology of psychiatric illness in general, and of affective disorders in particular, reveals a variety of associated biochemical abnormalities. These have generally been assumed to be part of the pathological process or secondary to it, and thus deserving of therapeutic efforts aimed at reversal. However, recent clinical and preclinical data suggest that some alterations occurring in the affective disorders may be compensatory and adaptive; that is, part of an endogenous therapeutic mechanism rather than part of the evolving disease process. For example, the symptom of sleep loss in depression seems to fall under this rubric inasmuch as sleep deprivation induces mood improvement in depressed patients. Preclinical data are presented that another primary pathological process--the occurrence of kindled seizures--can evoke endogenous compensatory processes that are either anticonvulsant in their own right, or enable the anticonvulsant effects of a drug such as carbamazepine. It may be that some biochemical abnormalities occurring in affective illness are similarly adaptive. As one example, increased thyrotropin-releasing hormone (TRH) has been reported in the cerebrospinal fluid (CSF) of depressed patients. This elevation of TRH and the resulting neuroendocrine profile may be part of an endogenous counter-regulatory process aimed at mood improvement. Again, preclinical seizure models are supportive in that TRH not only is induced following repeated seizures, but also exerts anticonvulsant effects on these same seizures. In an analogous fashion, TRH elevations in depressed patients may also exert ameliorating effects on depressive symptomatology. This formulation presents directly testable hypotheses that could importantly impact on our understanding of the pathophysiology of affective disorders, and suggests novel therapeutic strategies through the enhancement of endogenous compensatory mechanisms.
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PMID:Ziskind-Somerfeld Research Award 1992. Endogenous biochemical abnormalities in affective illness: therapeutic versus pathogenic. 144 65

The effects of gamma-butyrolactone-gamma-carbonyl-L-histidyl-L-propionamide citrate (DN-1417), a derivative of thyrotropin-releasing hormone, and liposome-entrapped DN-1417 (DN-L) were examined in amygdaloid-kindled rats. The animals were tested 2 h after intraperitoneal (i.p.) drug administration and then again every 24 h without further drug treatment. DN-1417 did not suppress the kindled seizure at 2 h but did beginning 1-6 days after injection. DN-L suppressed the kindled seizure at 2 h and had a more prolonged anticonvulsant effect than DN-1417. After liposomes were given i.p. once daily for 2 weeks, there was no morphologic evidence that liposomes damaged brain neurons. These results, together with previously published data, suggest that as drug delivery vehicles, liposomes can enhance the effectiveness of drugs in the CNS without producing overt brain damage.
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PMID:Anticonvulsant effect of DN-1417, a derivative of thyrotropin-releasing hormone, and liposome-entrapped DN-1417, on amygdaloid-kindled rats. 146 82

The effects of CNK-602A (N-[(6-methyl-5-oxo-3-thiomorpholinyl) carbonyl]-L-histidyl-L-prolinamide), a novel thyrotropin-releasing hormone related analog, were investigated on absence-like seizure and tonic convulsion in the spontaneously epileptic rat (SER), which is a genetically defined double-mutant. When CNK-602A of 0.2-1 mg/kg was given intravenously to the animal, there were no changes in the background EEG except for an increase in low-voltage fast waves concomitant with behavioral alertness. However, CNK-602A suppressed absence-like seizure and tonic convulsion in a dose-dependent manner for over 1 h. These antiepileptic effects of CNK-602A on both seizures were antagonized by pretreatment with haloperidol (1 mg/kg, i.p.). It was found, using a brain in vivo microdialysis method, that CNK-602A at a dose of 1 mg/kg, which inhibits the seizures, increased the release of dopamine in the caudate nucleus. These results suggest that CNK-602A inhibits the seizures of SER in a similar manner to thyrotropin-releasing hormone (TRH), probably by increasing the release of dopamine in the central nervous system. In addition, the antiepileptic effects of CNK-602A were more potent and lasted longer than those of TRH.
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PMID:Antiepileptic effects of CNK-602A, a novel thyrotropin-releasing hormone analog, on absence-like and tonic seizures of spontaneously epileptic rats. 147 66

We reported a female infant with early myoclonic encephalopathy (EME). She was diagnosed on the basis of clinical and laboratory features including electroencephalographic and magnetic resonance image (MRI) findings. Frequent erratic myoclonic seizures appeared since 28 days after birth and EEG showed a typical suppression-burst pattern. We administered a high-dose pyridoxal phosphate, thyrotropin-releasing hormone analogue (TRH), and then ACTH, but could not control the seizures at all. With seizure types, we observed the change from erratic myoclonus to tonic spasms in series, with concomitant EEG change to hypsarhythmia at the age of 6 months. Cranial MRI revealed delayed myelination in the white matter but no brain malformation. We administered ACTH to her again and succeeded partially in the decrease of the seizure frequency, and significantly in the improvement of EEG findings. It is supposed that the responsiveness to ACTH treatment changed with age as the seizure patterns developed from erratic myoclonus to tonic spasm.
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PMID:[A longitudinal study of clinical and electroencephalographic findings in a female infant with early myoclonic encephalopathy]. 165 45

The effect of DN-1417, a thyrotropin-releasing hormone (TRH) analogue, on photosensitivity and cortically kindled seizures was examined in seven Senegalese baboons (Papio papio). Intravenous (i.v.) administration of 2 mg/kg had no effect on either photosensitivity or cortically kindled seizures. When this agent was administered intracisternally, both the photomyoclonic response and cortically kindled seizures were suppressed for 4-5 days. A study of the transcallosal response also showed a long-lasting attenuation of the early positive wave (P1) amplitude (peak latency, 5-10 ms) elicited by a single stimulus after cisternal injection of DN-1417. These findings are consistent with the assumption that endogenous TRH is involved in suppression of epileptic seizures.
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PMID:Effect of DN-1417 on photosensitivity and cortically kindled seizure in Senegalese baboons, Papio papio. 189 19

Recent studies have demonstrated that intramuscular administration of thyrotropin-releasing hormone (TRH) or its analogue improves various clinical aspects of intractable epilepsy such as Lennox-Gastaut syndrome, West syndrome, and myoclonus epilepsy. Other clinical studies reported efficient property of intravenous TRH against status epilepticus. However, it is also true that intravenous TRH produces epileptic seizures in patients with epilepsy or organic brain damage. Thus, the utility of intravenous TRH for the treatment of status epilepticus seems to be equivocal. To further explore the problem in this regard, we examined the effect of TRH on limbic status epilepticus in rats. Thirty-eight male Wistar rats weighing 180-220g were used. Status epilepticus was induced by intracerebral injection of a combination of 200 micrograms of dibutyryl-cAMP (db-cAMP) and 67.2ng of ethylenediaminetetraacetic acid (EDTA) into the amygdala (AM) through an implanted cannula. 30 min later, TRH or vehicle (distilled water) was administered intravenously (i.v.) or intracerebroventricularly (i.c.v.). Although 3 mg/kg of TRH (n = 9), when injected i.v., did not alter the pattern of electroclinical ictal responses induced by db-cAMP/EDTA, 25 mg/kg (n = 5) and 50 mg/kg (n = 5) of TRH significantly exaggerated EEG and/or behavioral ictal seizures, beginning immediately after the injection and lasting for more than 30 min. With 50 mg/kg of TRH, the exaggerated seizure patterns were followed by marked suppression of electroclinical seizures. 50 micrograms of i.c.v. TRH (n = 5), like higher doses of i.v. TRH, caused a slight, but not a significant, build up of electroclinical ictal seizures, beginning immediately after the injection and lasting for about 30 min.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effects of thyrotropin-releasing hormone (TRH) on status epilepticus in rats]. 190 68

The effects of thyrotropin-releasing hormone (TRH) were investigated on absence-like seizures, which are characterized by the sudden appearance of 5-7 Hz spike-wave-like complexes in the cortical and hippocampal EEG, and on tonic convulsions of spontaneously epileptic rats (SER; zi/zi, tm/tm), a double mutant obtained by mating zitter homozygote (zi/zi) with tremor heterozygote rats (tm/+). TRH (5 and 10 mg/kg i.v.) inhibited the appearance of both absence-like seizures and tonic convulsions of SER without inducing obvious changes in the background EEG. The inhibitory effects were seen 5-20 min after injection of 10 mg/kg TRH and were antagonized by pretreatment with haloperidol (0.5 and 1.0/kg i.p.), although haloperidol alone did not affect the seizures. These results suggest that TRH has an antiepileptic effect in the genetically defined animal model, SER, and that the effect is mediated by the central dopaminergic system.
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PMID:Inhibition by thyrotropin-releasing hormone of epileptic seizures in spontaneously epileptic rats. 190 88


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