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 history, symptoms, diagnosis and treatment of phencyclidine hydrochloride (PCP) intoxication and the pharmacology of PCP are reviewed. Intoxication with low to moderate doses of PCP (5-20 mg) resembles an acute, confusional state generally lasting four to six hours. High doses (greater than 20 mg) may cause serious neurologic and cardiovascular complications and the patient is often comatose for several days. Treatment involves supportive psychological and medical measures. Evacuation of the stomach with activated charcoal and a saline cathartic may be indicated and succinylcholine chloride may ease intubation. Diazepam and chlorpromazine may be used to control the combative patient and the "PCP psychosis" patient, respectively. Antihypertensive agents are not usually needed, but diazoxide and hydralazine hydrochloride have been used to treat hypertensive crises. Diazepam and phenytoin have been used to treat seizures. Ion-trapping by continuous gastric suctioning and by urine acidification with ammonium chloride may increase clearance of PCP. Forced diuresis with furosemide in conjunction with acidification may further increase PCP clearance. Use of physostigmine is based on conjecture.
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PMID:Phencyclidine intoxication: a literature review. 36 Aug 32

Most street hallucinogens contain either LSD or phenycyclidine HCl (PCP). Because the acute phase of LSD and PCP mimic several other drugs and conditions, it is important to exclude these other possibilities. When faced with LSD or PCP, "talking down" usually suffices for the mild case; management becomes more complex should hyperpyrexia, coma, seizures or a hypertensive crisis ensue. Diazepam, not a phenothiazine, is preferred for sedation.
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PMID:Management of hallucinogen abuse. 106 15

Nervous system opportunistic infections are seen in about one fifth of AIDS cases and account for over 40% of the patients with neurological manifestations. Serious infections are seen in severely immunosuppressed patients, usually with CD4 counts of 200 ml-1 or less. The commonest is CMV, which can produce acute encephalitis, sometimes with focal hemisphere or brain-stem signs, dementia, retinitis, optic neuritis and an ascending radiculomyeloencephalitis. Cryptococcal meningitis is the most frequent fungal disease; a high degree of clinical suspicion is required in patients with fever, malaise, headache or seizures. Only CSF cultures are always positive; both serum and CSF cryptococcal antigen tests are highly sensitive and specific. Treatment with amphotericin B and flucytosine is successful in at least 70% of first episodes but side-effects are common. Without maintenance therapy 50% of patients relapse; fluconazole is recommended. Cerebral toxoplasmosis can present with focal cerebral or spinal cord signs but also as a diffuse encephalopathy; negative T. gondii serology is exceptional but positive serum titres are usually unhelpful. Treatment with sulfadiazine, pyrimethamine and folinic acid achieves good results in 90% of the first episodes, but side-effects are common. Appearances on CT scan or MRI may take several weeks to improve. The value of an empirical approach to treatment is well-established; an initial cerebral biopsy is difficult to justify. Without maintenance therapy a relapse rate of 50% can be expected; therapy with sulfadiazine and pyrimethamine may also prevent pneumocystosis. HIV disease appears to increase the likelihood of neurosyphilis, and the risk of relapse after conventional penicillin doses, in patients with syphilis; at least 3-4 weeks of appropriate therapy are recommended. A number of other diseases caused by viruses, fungi, bacteria and parasites are less common; these include progressive multifocal leukoencephalopathy, herpes simplex and zoster infections and tuberculosis.
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PMID:Central nervous system opportunistic infections in HIV disease: clinical aspects. 134 47

1-Phenylcyclohexylamine (PCA) and its analogues 1-phenylcyclopentylamine (PPA) and 1-(3-fluorophenyl)cyclohexylamine (3-F-PCA) are potent anticonvulsants in the mouse maximal electroshock (MES) seizure test. Unlike the structurally related dissociative anesthetic phencyclidine (PCP), however, which produces motor toxicity at anticonvulsant doses, PCA, PPA, and 3-F-PCA protect against MES seizures at 2.2- to 3.5-fold lower doses than those that cause motor toxicity when administered intraperitoneally (i.p.). In the present study, we evaluated the oral anticonvulsant activity of PCA, PPA, and 3-F-PCA in mice; we also examined 3-F-PCA in rats. All the compounds were orally active in the mouse MES seizure test (ED50 values 14.5, 53.4, and 26.7 mg/kg, respectively). Moreover, 3-F-PCA was especially potent in rats, either when administered i.p. (ED50 0.4 mg/kg vs. 9.4 mg/kg in mice) or orally (ED50 0.8 mg/kg). Surprisingly, however, oral PPA failed to cause motor toxicity in mice even at doses that were many times higher than those that were protective in the MES test (TD50 greater than 300 mg/kg). In rats, 3-F-PCA also showed a strikingly low oral toxicity (TD50 greater than 50 mg/kg) in relation to its potency as an anticonvulsant. Like PCP, PCA analogues block N-methyl-D-aspartate (NMDA)-induced behavioral effects and lethality in mice. Moreover, in vitro studies indicate that the compounds act as uncompetitive antagonists of the NMDA receptor-channel complex. Therefore, their anticonvulsant activity may, at least in part, relate to an interaction with NMDA receptors.
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PMID:Anticonvulsant 1-phenylcycloalkylamines: two analogues with low motor toxicity when orally administered. 153 Nov 30

Characteristics of muscarinic cholinergic (mACh), gamma-aminobutyric acid(A) (GABAA) and phencyclidine (PCP) receptors in the spontaneously epileptic rats (SER), which exhibit both absence-like seizures and tonic convulsion, were examined using in vitro quantitative autoradiography. Computer analysis using autoradiographic technique revealed that the amount of the specific binding of [3H]quinuclidinyl benzilate (QNB) to mACh receptors in the striatum of SER was more than that of zitter rats, not exhibiting both seizures and convulsion. However, the specific bindings of [3H]muscimol and [3H]N-(1-[2-thienyl]cyclohexyl)3,4-piperidine (TCP) to GABAA and PCP receptors, respectively, of SER were not different from those of zitter rats in various regions tested. These results suggest that hyperfunction of mACh receptors in the striatum is involved in the appearance of absence-like seizures and tonic convulsion of SER.
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PMID:Characteristics of muscarinic cholinergic, gamma-aminobutyric acid(A) and phencyclidine receptors in spontaneously epileptic rats; in vitro quantitative autoradiographic analysis. 166 11

Lamotrigine (LTG), a new anticonvulsant, chemically unrelated to current antiepileptic drugs (AEDs), resembles phenytoin (PHT) and carbamazepine (CBZ) in ability to block hindlimb extension in both the maximal electroshock test and leptazol-induced seizures. Results indicate that LTG may be of value in both partial and generalized seizures. In in vitro studies, LTG has been shown to inhibit veratrine-evoked release of glutamate when a threshold depolarizing concentration (4 micrograms/ml) is used, and also inhibits aspartate release when a larger stimulus is given (10 micrograms/ml). However, LTG does not block potassium-evoked transmitter release. LTG is a less potent inhibitor of the release of gamma-aminobutyric acid (GABA), acetylcholine, noradrenaline, and dopamine. LTG blocks the neurotoxicity of kainic acid in vivo, supporting the in vitro findings, and suggests that the anticonvulsant effect of LTG may be due to inhibition of glutamate release. In a test of working memory and phencyclidine (PCP) discrimination studies, LTG had no effect, indicating no sharing of the same PCP-like side effects associated with NMDA receptor blockade. In the gerbil model of global ischemia, high doses of LTG provided protection against damage to the CA1 region of the hippocampus. Analogues of LTG of higher potency to block the release of glutamate may be necessary to ensure protection against ischemic brain damage.
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PMID:Neurochemical and behavioral aspects of lamotrigine. 168 39

The effect of single administrations of MK-801 (5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine) or PCP (phencyclidine) on the induction of audiogenic seizure susceptibility by noise in immature rats was examined. Treatments with these non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists resulted in increases in noise exposure-dependent susceptibility. In neonatally drug-treated rats, seizures during adulthood were found to occur with significantly higher incidence and severity. Furthermore, drug treatments were found to lengthen what is normally a restricted developmental period within which susceptibility can be induced by noise exposure. The drugs, however, had no inherent ability to induce audiogenic seizure susceptibility if given alone. Moreover, in already-susceptible rats, MK-801 exhibited predictable anticonvulsant effects. These data suggest acute PCP or MK-801 exposures may transiently exacerbate risks inherent in certain forms of trauma. The mechanism underlying these effects is unknown although certain inferences are possible and may reveal much about epileptogenesis in this model.
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PMID:Sensitization to noise-mediated induction of seizure susceptibility by MK-801 and phencyclidine. 176 Jul 30

Pretreatment with metaphit (1-[1-(3-isothiocyanotophenyl)cyclohexyl]piperidine), a putative irreversible antagonist of phencyclidine (PCP) receptors, did not antagonize PCP-induced passive avoidance deficit in rats, and did not decrease [3H]MK-801 (5-methyl-10,11-dihydro-5H-dibenzocyclohepten-5,10-imine maleate) binding to PCP recognition sites coupled to NMDA receptors. The effectiveness of the metaphit treatment was evidenced by the occurrence of audiogenic seizures. These results suggest that previously reported antagonism in vivo actions of PCP by metaphit, is mediated by sites not involved in PCP-induced passive avoidance deficit, and not related to the NMDA receptor complex in brain structures studied (striatum, hippocampus, and cortex).
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PMID:Metaphit fails to antagonize PCP-induced passive avoidance deficit. 182 88

Recently, the presence of two high affinity binding sites for phencyclidine were described in guinea pig brain, with one site coupled to the glutamate excitatory amino acid receptor, specifically activated by N-methyl-D-aspartate (NMDA) (site 1) and the other site associated with the dopamine (DA) reuptake carrier (site 2). Phencyclidine and its analogs, as well as the benzomorphan opiates, are known to interact with binding sites for phencyclidine. In this study, the equilibrium dissociation constants (Kd) of these compounds for the two binding sites for phencyclidine were determined. Phencyclidine and 1-[1-(2-thienyl)cyclohexyl]piperidine (TCP), an analog of PCP, were essentially non-selective between the two sites and also were the two drugs of the group observed to have the highest affinity for site 2. (+)-5-Methyl-10,11-dihydro-5H-dibenzo[a,d]cycloheptene-5,10-imine [(+)MK801] was the most selective agent for site 1, while none of the drugs tested showed selectivity for site 2. In humans, phencyclidine produces psychotomimetic effects, while (+)MK801 has been reported to produce minimal, if any, psychotomimetic effects, at doses sufficient to reduce seizures. These clinical observations, in conjunction with the present biochemical binding data, suggest that (+)MK801 may serve as a "marker" for site 1 and that the psychotomimetic effects of phencyclidine might be mediated by site 2.
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PMID:Specificity of phencyclidine-like drugs and benzomorphan opiates for two high affinity phencyclidine binding sites in guinea pig brain. 196 80

There are several protozoan infections that cause relatively benign illness in normal individuals but result in severe disease manifestations in patients with AIDS. These diseases include Pneumocystis carinii pneumonia, CNS toxoplasmosis, cryptosporidiosis, and isosporiasis. Pneumocystis carinii pneumonia (PCP) caused by Pneumocystis carinii, is the most common opportunistic infection in AIDS. It is seen in more than 80% of individuals with this syndrome. Although historically classified as a protozoan, this organism shares many biochemical characteristics with fungi. The onset of PCP may be insidious, and cough and dyspnea are the most common presenting symptoms. Auscultation of the lungs is often unremarkable, but diffuse infiltrates are commonly seen on chest radiographs. The diagnosis of PCP can be confirmed by identifying the organism on specimens obtained by sputum induction or bronchoalveolar lavage. Trimethaprim-sulfamethoxazole is the treatment of choice but is unfortunately associated with leukopenia and rash in many individuals. Both trimethaprim-sulfamethoxazole and aerosolized pentamidine are used prophylactically in patients at high risk for initial or relapsing infection. The appropriate use of these agents has resulted in improved survival for AIDS patients with PCP. Toxoplasmosis, due to Toxoplasma gondii, affects the central nervous system in patients with AIDS. Headache is a common presenting symptom, and both seizures and paresis can occur. A diagnosis of toxoplasmosis is strongly suspected in symptomatic individuals with ringed mass lesions noted on head CT. Patients with this condition are treated with a combination of sulfadiazine, pyrimethamine, and folinic acid. Cryptosporidiosis and isosporiasis are coccidian protozoan diseases that can result in severe, acute, and chronic diarrhea in immunocompromised individuals. Cryptosporidiosis is the more common of the two and is caused by an unknown species of the genus crytosporidium. Isosporiasis is due to infection with Isospora belli. Dehydration and weight loss are a common result of infection with either agent. A definitive diagnosis can be made by examining an acid fast stain of a diarrheal stool specimen and demonstrating oocysts that are specific for each of these organisms. Fluid replacement and general supportive care are essential in the treatment of both of these diseases. Spiramycin is an unproven treatment modality that is often used in patients with cryptosporidiosis. Isosporiasis responds to initial therapy with trimethaprim-sulfamethoxazole, followed by prophylaxis with pyrimethamine. The adoption of safe sexual practices that minimize fecal-oral contamination should decrease the future prevalence of these diseases and other enteric parasitic infections.
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PMID:Parasitic diseases. Diseases associated with acquired immunodeficiency syndrome. 201 33


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