RESUMO
Frontal lobe dysfunction is widely suspected to underlie negative symptoms of schizophrenia. This hypothesis is based largely on long-standing observations of the similarities between the effects of frontal lobe lesions and negative symptoms. However, there is little direct evidence specifically for such an association in schizophrenic patients. We measured the relationship between decreased relative prefrontal cortex glucose metabolism (hypofrontality) using positron emission tomography and evaluated the severity of negative symptoms in 20 chronic schizophrenics who underwent scanning while not receiving neuroleptic drugs. We found a close relationship between negative symptoms and prefrontal hypometabolism, particularly in the right dorsolateral convexity. This association was regionally specific. Furthermore, there was no evidence that this relationship was an artifact of age, cerebral atrophy, or severity of positive symptoms.
Assuntos
Lobo Frontal/metabolismo , Glucose/metabolismo , Esquizofrenia/diagnóstico , Psicologia do Esquizofrênico , Adulto , Antipsicóticos/uso terapêutico , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Doença Crônica , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Esquizofrenia/metabolismo , Índice de Gravidade de Doença , Tomografia Computadorizada de Emissão , Tomografia Computadorizada por Raios XRESUMO
A one-to-one relationship between clinical antipsychotic potency and pharmacologic dopaminergic antagonism is implicit in the dopamine hypothesis of neuroleptic action. Thiethylperazine maleate, a classical antiemetic phenothiazine, displays dopaminergic antagonism in behavioral, neurochemical, and neuroendocrine systems, but is paradoxical insofar as it is thought not to possess clinical neuroleptic activity. In three tests of dopaminergic antagonism--elevation of levels of CSF homovanillic acid in monkeys, striatal dihydroxyphenylacetic acid in rats, and prolactin in man--as well as in a clinical trial of neuroleptic efficacy in schizophrenics, thiethylperazine was fully active and approximately three times as potent as chlorpromazine. Differences in efficacy between this and earlier clinical studies can be accounted for on the basis of dosage.
Assuntos
Antagonistas de Dopamina , Esquizofrenia/tratamento farmacológico , Tietilperazina/farmacologia , Ácido 3,4-Di-Hidroxifenilacético/antagonistas & inibidores , Ácido 3,4-Di-Hidroxifenilacético/isolamento & purificação , Adenilil Ciclases/fisiologia , Animais , Corpo Estriado/análise , Dopamina/metabolismo , Haplorrinos , Ácido Homovanílico/líquido cefalorraquidiano , Humanos , Macaca mulatta , Masculino , Prolactina/sangue , Ratos , Tietilperazina/metabolismoRESUMO
Seven normal subjects received 0.25 mg/kg D-amphetamine orally, both after an overnight fast and again after a standard breakfast. Plasma levels, subjective and cardiovascular effects, and observer-rated activation were assessed hourly for 5 hr. Food did not affect amphetamine levels. Plasma levels peaked at 2-3 hr. Maximum cardiovascular effects generally occurred at 1 hr, whereas maximum behavioral and subjective effects occurred at 2 hr. Subjective and behavioral effects declined thereafter, in spite of substantial amphetamine levels. A separate group of 8 subjects received 0.5 mg/kg D-amphetamine orally. Plasma levels, subjective and cardiovascular effects, and activation ratings were assessed hourly for 4 hr. Maximum plasma levels were approximately twice those seen in the first group. In this case, plasma levels peaked at 3-4 hr; blood pressure and subjective and behavioral effects were all maximal at 2-3 hr and were declining by 4 hr, in spite of stable or rising plasma levels.
Assuntos
Nível de Alerta/efeitos dos fármacos , Dextroanfetamina/farmacocinética , Administração Oral , Adulto , Dextroanfetamina/farmacologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Changes in plasma homovanillic acid (HVA) were investigated in neuroleptic responsive and nonresponsive schizophrenics in order to delineate parameters of dopamine regulation, which may underlie differences in neuroleptic responsivity. Nineteen schizophrenics were treated with haloperidol for 6 weeks. HVA was sampled at baseline, 24 hr after initial neuroleptic dose, and after 6 weeks of treatment. Subjects were pretreated with debrisoquin in order to reduce the peripheral production of HVA. The responders had an initial rise in HVA at 24 hr after first neuroleptic dose, followed by a decline back to baseline over the 6 weeks of treatment. The nonresponders' HVA failed to rise at 24 hr after first neuroleptic dose. At 6 weeks of treatment their HVA had fallen to significantly below baseline. Thus, a rise in HVA 24 hr after the first dose of neuroleptic predicted treatment response; a fall in HVA at 6 weeks to below pretreatment values was associated with neuroleptic nonresponse.
Assuntos
Haloperidol/administração & dosagem , Ácido Homovanílico/sangue , Esquizofrenia/tratamento farmacológico , Psicologia do Esquizofrênico , Adulto , Análise de Variância , Relação Dose-Resposta a Droga , Esquema de Medicação , Haloperidol/efeitos adversos , Haloperidol/farmacocinética , Humanos , Masculino , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Psicometria , Receptores Dopaminérgicos/efeitos dos fármacos , Receptores Dopaminérgicos/fisiologia , Esquizofrenia/sangueRESUMO
We measured serum phospholipase A2 (PLA2) activity in 39 schizophrenics, 26 psychiatric controls, and 26 normal controls using a radioenzymatic assay with phosphatidylcholine as precursor. Serum PLA2 activity was significantly higher in schizophrenics (p = 0.002) and other psychiatric (including substance abusing) patients (p = 0.032) than in normal controls. Enzyme activity did not differ between the schizophrenic patients and psychiatric controls. Fifty-one percent of the schizophrenics and 46% of psychiatric controls had PLA2 values above the highest value for normal controls. In the psychiatric control group higher than normal PLA2 activities were observed in all diagnostic categories, including major depression, bipolar disorder, posttraumatic stress disorder (PTSD), and substance abuse. In the context of others' findings of increased circulating PLA2 in infectious and inflammatory conditions, these increases must be viewed as disease nonspecific. The significance of these changes and their relationship to other acute-phase protein changes needs to be clarified in future research.
Assuntos
Transtornos Mentais/enzimologia , Fosfolipases A/sangue , Esquizofrenia/enzimologia , Psicologia do Esquizofrênico , Adulto , Feminino , Humanos , Masculino , Transtornos Mentais/diagnóstico , Transtornos Mentais/psicologia , Pessoa de Meia-Idade , Fosfatidilcolinas/sangue , Fosfolipases A2 , Escalas de Graduação Psiquiátrica , Valores de Referência , Esquizofrenia/diagnósticoRESUMO
The effects of d-amphetamine (0.5 mg/kg orally) on regional cerebral glucose utilization were measured with positron emission tomography (PET) in 17 schizophrenics (along with a placebo-control group of an additional six schizophrenic patients). The acute d-amphetamine challenge tended to decrease glucose utilization throughout much of the brain, with a regional effect that was statistically significant in the left temporal cortex. There was no apparent relationship between the effects of amphetamine-induced changes in regional cerebral metabolism and psychotic symptom exacerbation. An exploratory analysis suggested that features characteristic of Crow's type II syndrome were significant predictors of cerebral hyporesponsivity to stimulant challenge, however.
Assuntos
Glicemia/metabolismo , Córtex Cerebral/efeitos dos fármacos , Dextroanfetamina , Esquizofrenia/diagnóstico por imagem , Psicologia do Esquizofrênico , Tomografia Computadorizada de Emissão , Nível de Alerta/efeitos dos fármacos , Nível de Alerta/fisiologia , Córtex Cerebral/diagnóstico por imagem , Dominância Cerebral/efeitos dos fármacos , Dominância Cerebral/fisiologia , Método Duplo-Cego , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Esquizofrenia/induzido quimicamente , Esquizofrenia/diagnóstico , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/efeitos dos fármacosRESUMO
In an open study of 8 subjects, approximately half showed some attenuation of CNS stimulant effects of amphetamine after pretreatment with lithium. Two showed specific blockade of euphoria, with persistence of some CNS stimulant effects. In 3 subjects lithium did not appear to affect the response to amphetamine. Lithium caused significant attenuation of the amphetamine-induced increase in systolic blood pressure for the group as a whole.
Assuntos
Dextroanfetamina/antagonistas & inibidores , Lítio/farmacologia , Adulto , Pressão Sanguínea/efeitos dos fármacos , Dextroanfetamina/farmacologia , Euforia/efeitos dos fármacos , Feminino , Humanos , Lítio/sangue , Masculino , Pessoa de Meia-Idade , Pré-Medicação , Comportamento Verbal/efeitos dos fármacosRESUMO
Six hospitalized patients with neuroleptic-induced akathisia were treated with clonidine under single-blind conditions. Akathisia and anxiety at maximum clonidine dose were significantly lower than at baseline, although it was difficult to differentiate specific therapeutic effects from sedation.
Assuntos
Antipsicóticos/efeitos adversos , Clonidina/uso terapêutico , Agitação Psicomotora/tratamento farmacológico , Adulto , Acatisia Induzida por Medicamentos , Ansiedade/induzido quimicamente , Ansiedade/tratamento farmacológico , Clonidina/administração & dosagem , Hospitalização , Humanos , Masculino , Transtornos Mentais/tratamento farmacológico , Pessoa de Meia-Idade , Projetos Piloto , SonoRESUMO
Alprazolam added to stable doses of neuroleptics in nine schizophrenic patients was associated with a 20%-30% mean reduction in positive and negative symptoms, although clinical response was variable and in some patients particularly brisk. The authors examined the possibilities of a pharmacokinetic effect of alprazolam on neuroleptic plasma levels and of a clinical effect of alprazolam. The modest increase in mean neuroleptic plasma levels did not correlate with clinical change, but those patients with the highest alprazolam plasma levels tended to show more robust clinical responses.
Assuntos
Alprazolam/farmacocinética , Antipsicóticos/farmacocinética , Esquizofrenia/tratamento farmacológico , Adulto , Alprazolam/sangue , Alprazolam/uso terapêutico , Antipsicóticos/sangue , Antipsicóticos/uso terapêutico , Doenças dos Gânglios da Base/induzido quimicamente , Sinergismo Farmacológico , Quimioterapia Combinada , Discinesia Induzida por Medicamentos/etiologia , Feminino , Flufenazina/sangue , Flufenazina/farmacocinética , Flufenazina/uso terapêutico , Haloperidol/sangue , Haloperidol/farmacocinética , Haloperidol/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Esquizofrenia/sangue , Psicologia do EsquizofrênicoRESUMO
OBJECTIVE: The authors studied the effects of vitamin E treatment of tardive dyskinesia; earlier studies have produced contradictory results. METHOD: Twenty-eight patients with tardive dyskinesia were treated in a double-blind, parallel-group comparison study of 8-12 weeks of treatment with vitamin E (1600 IU/day) or matching placebo capsules. RESULTS: The Abnormal Involuntary Movement Scale scores of the patients treated with vitamin E improved significantly compared to the scores of the patients given placebo. CONCLUSIONS: These results support earlier findings of the efficacy of vitamin E in treating tardive dyskinesia.
Assuntos
Discinesia Induzida por Medicamentos/tratamento farmacológico , Vitamina E/uso terapêutico , Assistência Ambulatorial , Antipsicóticos/efeitos adversos , Método Duplo-Cego , Discinesia Induzida por Medicamentos/etiologia , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Placebos , Esquizofrenia/tratamento farmacológicoRESUMO
Prolactin levels were determined in plasma samples obtained before and after administration of apomorphine or L-dopa to otherwise unmedicated chronic schizophrenic patients or control subjects. Basal prolactin levels did not differ in these two groups. Suppression of prolactin levels after each dopamine agonist was highly significant. Suppression in schizophrenics was slightly less than in controls following apomorphine and slightly greater following L-dopa. The authors discuss the implications of these findings as well as the limitations of the prolactin regulatory system as an index of dopamine agonist sensitivity.
Assuntos
Apomorfina/farmacologia , Levodopa/farmacologia , Prolactina/sangue , Esquizofrenia/sangue , Adulto , Doença Crônica , Depressão Química , Dopamina/fisiologia , Humanos , Masculino , Esquizofrenia/fisiopatologiaRESUMO
Frontal/posterior ratios of cerebral glucose metabolism as determined by positron emission tomography were significantly lower in 13 chronic schizophrenic patients than in eight normal control subjects, as were absolute metabolic rates in both the frontal and posterior regions. The differences were not accounted for by cerebral atrophy.
Assuntos
Lobo Frontal/metabolismo , Glucose/metabolismo , Esquizofrenia/metabolismo , Adulto , Atrofia , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Encéfalo/patologia , Doença Crônica , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Esquizofrenia/diagnóstico , Tomografia Computadorizada de Emissão , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: The authors' goals were to determine whether baseline dopamine activity contributes to response to methylphenidate and to assess the pattern of metabolic responses associated with enhanced dopamine activity. METHOD: They used positron emission tomography with 2-deoxy-2[18F]fluoro-D-glucose to evaluate the effects of two sequential doses of methylphenidate on brain metabolism in 15 healthy subjects. Dopamine D2 receptor availability was measured with [11C]raclopride to evaluate its relation to methylphenidate-induced metabolic changes. RESULTS: Methylphenidate increased brain metabolism in six subjects, decreased it in two, and did not change it in seven; however, it consistently increased cerebellar metabolism. Methylphenidate significantly increased "relative" (region relative to the whole brain) metabolism in the cerebellum and decreased it in the basal ganglia. Regional metabolic changes in the cerebellum and the frontal and temporal cortices were significantly correlated with D2 availability. Frontal and temporal metabolism were increased in subjects with high D2 receptors and decreased in subjects with low D2 receptors. CONCLUSIONS: Methylphenidate induced variable changes in brain metabolism, but it consistently increased cerebellar metabolism. It also induced a significant reduction in relative metabolism in the basal ganglia. The significant association between metabolic changes in the frontal and temporal cortices and in the cerebellum and D2 receptors suggests that methylphenidate's metabolic effects in these brain regions are due in part to dopamine changes and that differences in D2 receptors may be one of the mechanisms accounting for the variability in response to methylphenidate.
Assuntos
Encéfalo/metabolismo , Glucose/metabolismo , Metilfenidato/farmacologia , Receptores de Dopamina D2/metabolismo , Adulto , Gânglios da Base/diagnóstico por imagem , Gânglios da Base/efeitos dos fármacos , Gânglios da Base/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Radioisótopos de Carbono , Cerebelo/diagnóstico por imagem , Cerebelo/efeitos dos fármacos , Cerebelo/metabolismo , Desoxiglucose/análogos & derivados , Relação Dose-Resposta a Droga , Fluordesoxiglucose F18 , Lobo Frontal/efeitos dos fármacos , Lobo Frontal/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Racloprida , Receptores de Dopamina D2/efeitos dos fármacos , Salicilamidas , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/efeitos dos fármacos , Lobo Temporal/metabolismo , Tomografia Computadorizada de EmissãoRESUMO
OBJECTIVE: The purpose of this report was to determine 1) the effects of chronic haloperidol treatment on cerebral metabolism in schizophrenic patients, 2) the relation between negative symptoms and haloperidol-induced regional changes in cerebral glucose utilization, and 3) the relation between metabolic change and clinical antipsychotic effect. METHOD: Cerebral glucose utilization, as determined by position emission tomography (PET), was studied in 18 male schizophrenic subjects before and after chronic treatment with haloperidol at a standardized plasma level. RESULTS: Overall, haloperidol caused a widespread decrease in absolute cerebral glucose metabolism. The cerebral metabolic response to haloperidol was blunted in patients with high pretreatment negative symptom scores. CONCLUSIONS: Taken together with the results from a previously reported PET study of the effects of an acute amphetamine challenge (in which 14 of the current subjects participated), these data suggest that the negative symptom complex is associated with diminished cerebral response to change in dopaminergic activity. This deficit cannot be solely accounted for by structural differences.
Assuntos
Encéfalo/metabolismo , Glucose/metabolismo , Haloperidol/uso terapêutico , Esquizofrenia/tratamento farmacológico , Psicologia do Esquizofrênico , Adulto , Anfetaminas/farmacologia , Encéfalo/efeitos dos fármacos , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Haloperidol/farmacologia , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Receptores Dopaminérgicos/efeitos dos fármacos , Esquizofrenia/diagnóstico , Esquizofrenia/metabolismo , Tomografia Computadorizada de Emissão , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: The authors have shown that decreases in dopamine D2 receptors in cocaine abusers were associated with decreased metabolism in the cingulate and prefrontal and orbitofrontal cortices. To assess whether increasing dopamine would reverse these metabolic decrements, they measured the effects of methylphenidate, a drug that increases dopamine, on brain glucose metabolism in 20 cocaine abusers. METHOD: The subjects underwent two [18F]fluorodeoxyglucose positron emission tomography scans, one after two sequential placebo injections and one after two intravenous doses of methylphenidate. D2 receptors were measured with [11C]raclopride to evaluate their relation to methylphenidate-induced metabolic changes. RESULTS: Methylphenidate induced variable changes in brain metabolism: subjects with the higher D2 measures tended to increase metabolism, whereas those with the lower D2 measures tended to decrease metabolism. Methylphenidate's effects were significant for increases in metabolism in the superior cingulate, right thalamus, and cerebellum. Methylphenidate-induced changes in the right orbitofrontal cortex and right striatum were associated with craving, and those in the prefrontal cortex were associated with mood. CONCLUSIONS: Although methylphenidate increased metabolism in the superior cingulate, it only increased metabolism in orbitofrontal or prefrontal cortices in the subjects in whom it enhanced craving and mood, respectively. This indicates that dopamine enhancement is not sufficient per se to increase metabolism in these frontal regions. Activation of the right orbitofrontal cortex and right striatum (brain regions found to be abnormal in compulsive disorders) in the subjects reporting craving may be one of the mechanisms underlying compulsive drug administration in addicted persons. The predominant correlation of craving with right but not left brain regions suggests laterality of reinforcing and/or conditioned responses.
Assuntos
Comportamento Aditivo/induzido quimicamente , Córtex Cerebral/metabolismo , Transtornos Relacionados ao Uso de Cocaína/metabolismo , Dopamina/metabolismo , Metilfenidato/farmacologia , Adulto , Comportamento Aditivo/diagnóstico por imagem , Comportamento Aditivo/metabolismo , Química Encefálica/efeitos dos fármacos , Radioisótopos de Carbono , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/efeitos dos fármacos , Transtornos Relacionados ao Uso de Cocaína/diagnóstico por imagem , Transtornos Relacionados ao Uso de Cocaína/psicologia , Condicionamento Psicológico/efeitos dos fármacos , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Antagonistas de Dopamina , Fluordesoxiglucose F18 , Lateralidade Funcional/efeitos dos fármacos , Lateralidade Funcional/fisiologia , Glucose/metabolismo , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/efeitos dos fármacos , Giro do Cíngulo/metabolismo , Humanos , Masculino , Racloprida , Receptores de Dopamina D2/efeitos dos fármacos , Receptores de Dopamina D2/metabolismo , Reforço Psicológico , Salicilamidas , Tomografia Computadorizada de EmissãoRESUMO
Thirty patients with primary cocaine dependence who had used cocaine within the past 24 hours and were being admitted to a detoxification ward were rated for signs and symptoms of cocaine abstinence and craving. They then received four doses of either L-dihydroxy-phenylalanine/carbidopa (100 mg/25 mg) or placebo over the next day. Ratings were repeated in the late afternoon of the day of admission and after the final morning dose the next day. No significant differences in abstinence scores were found between the two treatment groups. The lack of drug-placebo differences appeared to be mainly due to rapid clearing of abstinence symptoms in the placebo-treated patients.
Assuntos
Carbidopa/uso terapêutico , Cocaína , Levodopa/uso terapêutico , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Adulto , Testes Respiratórios , Combinação de Medicamentos , Eletrocardiografia/efeitos dos fármacos , Humanos , Síndrome de Abstinência a Substâncias/psicologiaRESUMO
Patients in inpatient rehabilitation for uncomplicated cocaine dependence were asked whether, compared with the time of their first regular use, they could now identify changes in the effects of similar doses of cocaine. We asked about a spectrum of cocaine effects "then" and "now" and whether the same amount of drug caused effects to occur to about the same degree, less intensely (tolerance), or more intensely (sensitization). Nearly half our sample developed predominantly paranoid psychoses in the context of cocaine use. Sensitization was consistently linked only to psychosis-related cocaine effects. It has been proposed that mesolimbic dopaminergic sensitization might contribute to addiction severity. A preliminary followup of patients who were sensitized or nonsensitized to psychosis development suggests that rehospitalization for treatment of addiction may be more frequent in the sensitized group.
Assuntos
Cocaína , Entorpecentes , Transtornos Relacionados ao Uso de Opioides/psicologia , Psicoses Induzidas por Substâncias/psicologia , Adulto , Biomarcadores , Cocaína Crack , Feminino , Humanos , Masculino , Transtornos Paranoides/induzido quimicamente , Transtornos Paranoides/psicologia , RecidivaRESUMO
d-Propranolol lacks clinically significant beta-adrenergic receptor blocking properties, but has the same membrane stabilizing effects as racemic (d,l) propranolol. To assess the role of beta-blockade versus membrane stabilization or other shared nonspecific effects in the therapeutic action of propranolol in neuroleptic-induced akathisia (NIA) we treated 11 patients with NIA in a crossover, double-blind study of d-propranolol versus placebo. Akathisia scores were unchanged after both d-propranolol and placebo. Eight patients were subsequently treated in a nonblind manner with racemic propranolol, with a significant reduction in akathisia scores. These findings suggest that beta-blockade, not membrane stabilization or other shared nonspecific effects, contributes to the efficacy of propranolol in NIA.
Assuntos
Acatisia Induzida por Medicamentos , Antipsicóticos/efeitos adversos , Propranolol/uso terapêutico , Adulto , Pressão Sanguínea , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Agitação Psicomotora/tratamento farmacológico , Agitação Psicomotora/fisiopatologiaRESUMO
The clinical similarities between PCP psychosis and schizophrenia have contributed importantly to the development of the glutamate hypothesis of schizophrenia. Sensory gating, as measured by prepulse inhibition of the acoustic startle reflex (PPI), is impaired in patients with schizophrenia. In animals, the noncompetitive NMDA antagonists PCP and ketamine disrupt PPI in a way that resembles the defect seen in schizophrenia. The purpose of this work is to investigate the modulation of sensory gating in humans by subanaesthetic doses of ketamine. 16 healthy male subjects received a 60-min infusion of ketamine (0.5 mg/kg) or normal saline on two separate days in a randomized double-blind crossover design. Clinical ratings and PPI were done during the infusion on both days. Ketamine produced robust clinical effects. Dissociative symptoms as measured by the CADSS increased from 0 +/- 0.0 to 29.3 +/- 14.3; negative symptoms (Affect Rating Scale) increased from 17.2 +/- 0.8 to 24.8 +/- 3.1; and total BPRS scores increased from 18.3 +/- 0.8 to 26.4 +/- 5.1. ANOVAs for these ratings were all significant at the p <.000 level, although BPRS increases were not in the range seen in decompensated schizophrenic patients. The amplitudes of the startle responses to pulse-alone stimuli were not significantly different on ketamine and placebo days. Ketamine did not cause disruption in PPI as expected. On the contrary, in the first block of the PPI session ketamine significantly enhanced PPI (ANOVA; F=6.15, p =.026). These results indicate that the clinical effects of ketamine are not coupled with schizophrenic-like disruption of PPI in normal controls.
Assuntos
Antagonistas de Aminoácidos Excitatórios/efeitos adversos , Ketamina/efeitos adversos , Inibição Neural/efeitos dos fármacos , Reflexo de Sobressalto/efeitos dos fármacos , Adulto , Afeto/efeitos dos fármacos , Afeto/fisiologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Fenômenos Fisiológicos Cardiovasculares/efeitos dos fármacos , Antagonistas de Aminoácidos Excitatórios/administração & dosagem , Ácido Glutâmico/metabolismo , Alucinações/induzido quimicamente , Alucinações/fisiopatologia , Humanos , Ketamina/administração & dosagem , Masculino , Inibição Neural/fisiologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Testes Neuropsicológicos , Tempo de Reação/efeitos dos fármacos , Tempo de Reação/fisiologia , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Receptores de N-Metil-D-Aspartato/metabolismo , Valores de Referência , Reflexo de Sobressalto/fisiologiaRESUMO
Nine hospitalized schizophrenic patients with tardive dyskinesia were treated with the calcium-channel antagonist verapamil under single-blind conditions. The tardive dyskinesia and activation scores decreased, and the anxiety/depression scores increased. The changes were small but statistically significant.