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At least 919 records · Page 51Linked to original sources
PubMed1990

Pathophysiologic basis for schizophrenia and the efficacy of antipsychotics.

Current concepts of schizophrenia and its treatment are discussed. Schizophrenia entails negative symptoms, such as behavioral and cognitive deficits, attributed to loss of normal functions, and positive, or florid, symptoms that originate from the disturbed function of the remainder of the brain. Schizophrenia type I has positive symptoms predominating, and schizophrenia type II has negative symptoms predominating. Many atypical antipsychotics are now in Phase II and Phase III development; the prototype, clozapine, is now available. These agents challenge traditional views about drug treatment in schizophrenia. Schizophrenia may be explained by a persistent impairment in one or more neurotransmitter or neuromodulatory regulatory mechanisms, resulting in unstable or erratic neurotransmission. A more complex conceptualization of the role of the dopaminergic system makes it possible to understand the lack of biochemical tolerance to the therapeutic effects of antipsychotics, the varied time to onset of effects and prevalence of extrapyramidal symptoms, and the differences in efficacy within and among patients. Drug selection on the basis of patient-specific biological markers and neuropsychological function might expedite treatment responses. Drug therapy should augment homeostatic mechanisms and restore appropriate dopaminergic responses to physiological stimuli. Atypical antipsychotics may act by stabilizing presynaptic activity at a new set point, activating prefrontal dopaminergic systems and inhibiting mesolimbic systems, or exerting pharmacologic or functional effects on other neurotransmitter and neuropeptidergic systems. The traditional view that schizophrenia is simply a manifestation of dopaminergic overactivity is inadequate. New investigative techniques and the study of atypical antipsychotics suggest that a dysregulation hypothesis may be more consistent with the complexities of schizophrenia.

Antipsychotic Agents↗
PubMed1978

[Convergence of reticulo-, vestibulo- and rubrospinal influences on motor neurons of the cervical region of the cat spinal cord].

Intracellular recording of synaptic potentials of 93 cervical motoneurons was performed in cats under stimulation of medial longitudinal fasciculus, Deiters vestibular nucleus and red nucleus. Under stimulation of medial longitudinal fasciculus and Deiters nucleus in motoneurons of the forelimb muscles distal groups excitatory reactions were predominant and in motoneurons of proximal extensors inhibitory reactions prevailed. When stimulating the red nucleus excitatory and inhibitory reactions were recorded almost in equal number of cells independently of functional significance of corresponding muscles. Monosynaptic EPSPs were recorded in 1/5 of motoneurons under stimulation of the medial longitudinal fasciculus and only in several cases during stimulation of vestibular and red nuclei. In the other cases stimulation of the structures investigated caused polysynaptic reactions in motoneurons which arose after a series of 2-3 stimuli. In 62% of motoneurons when stimulating different structures under study the reactions were of the same direction. The mutual facilitation of reactions was revealed under stimulation of different inputs. The data obtained show that interaction of influences of the studied structures occurs to a considerable extent at the level of spinal interneurons.

Animals↗
PubMedDate not supplied

[Central mechanisms of the development of motor disorders during human aging].

This paper deals with the functional state of the brain and its descending regulatory influences on the brain stem-spinal formations in the elderly. The role of changes revealed in the formation of the clinical syndrome of age-related extrapyramidal insufficiency (EPI) as a risk factor of Parkinson's disease, has been shown. 274 apparently healthy subjects aged from 20 to 102 and 136 patients with early stages of Parkinson's disease were examined. The program of the neurophysiological investigation included: frequency-integrative analysis of EEG, visual and somatosensory potentials, simple motor reaction time and stimulating electroneuromyography (H reflex). It has been found that in aging and in Parkinson's disease one-directional changes in the CNS function that form age-related and pathologic EPI occur. The complex of neurophysiological indices is a reflection of the CNS influence on the underlying spinal formations, and it can be used for early diagnostics of the motor disorders in aging.

Adult↗
PubMed1989

[Effects of substance P on experimental parkinsonian syndrome].

The aim of this study was to investigate the effect of substance P (SP) on parkinsonian syndrome and the generator of pathologically enhanced excitation (GPEE) in the caudate nuclei (CN). Repeated i. p. administration of MPTP in 12 month rats induced oligokinesia and rigidity followed by the high amplitude slow and rapid waves in both CN. The changes of electrical activity in CN were more prominent than in the sensorimotor cortex. The bilateral intracaudate injection of SP (5 micrograms) resulted in an increase in motor activity and almost completely abolished the rigidity. The reduction of extrapyramidal symptoms was considered as a result of the inhibition of GPEE. The changes of the SP balance in nigro-striatal system was suggested to be one of the pathogenetic links of parkinsonian syndrome.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1989

Effects of ICI 169,369, a selective serotonin2 antagonist, in electrophysiological tests predictive of antipsychotic activity.

Extracellular single unit recording techniques were used to compare the effects of ICI 169,369, a selective serotonin2 receptor antagonist, with the reference antipsychotic (AP) agents clozapine and haloperidol, in electrophysiological tests that may predict AP activity. ICI 169,369 was found to reverse the inhibitory actions of amphetamine on A9 and A10 dopamine (DA) neurons, a common property shared by other AP drugs, and was comparable in potency to clozapine. In cell population studies, acute treatment with ICI 169,369 (at a low dose only) and clozapine selectively increased the number of spontaneously active A10 DA cells, which was found to correlate with the ability of both these drugs to cause depolarization inactivation (DI) of A10 DA cells after chronic administration. Interestingly, chronic treatment with ICI 169,369 also caused a significant increase in the number of actively discharging A9 DA cells, an effect not predicted on the basis of the acute data. A similar effect was noted for clozapine, although the magnitude did not reach statistical significance. This profile of activity was unlike that of haloperidol, which acutely caused a nonselective increase in the number of active A9 and A10 DA cells, associated with the ability of this agent to cause DI of both A9 and A10 DA cells after chronic treatment. Inasmuch as DI of A10 DA cells may be correlated with AP efficacy whereas DI of A9 DA cells may predict the ability of an AP to cause extrapyramidal side effects, ICI 169,369, like clozapine, may be a potential AP with a reduced likelihood for producing extrapyramidal side effects.

Action Potentials↗
PubMed1989

Extrapyramidal side effects caused by fluphenazine decanoate in a horse.

To provide long-term sedation, a horse was given fluphenazine decanoate, a human antipsychotic drug. The horse was progressively agitated and made unusual repetitive motions. Sedation with barbiturates was an effective treatment. This case is not unusual, and the use of fluphenazine by veterinarians in horses as a mild long-acting tranquilizer is not uncommon.

Animals↗
PubMed1987

Clinical electroencephalographic variables suggesting extrapyramidal side effect risk.

Previous work has suggested that paroxysmal EEG dysrhythmias in psychiatric patients may be associated with an increased incidence of such diverse side effects as dyskinetic movements, extrapyramidal symptoms, iatrogenic seizures, and somatic/affective effects of oral contraceptives. The new analyses presented here extend these observations by using a large sample of 375 neuroleptically treated psychiatric patients with independently secured awake and asleep admission EEG studies. Those patients with minor paroxysmal EEG dysrhythmias are much more likely than normal EEG patients to receive anti-EPS medication during their treatment program. Furthermore, using data obtained from direct examination for EPS signs, neuroleptically treated patients with paroxysmal dysrhythmias as contrasted with those with normal EEGs, display statistically significant increases in EPS symptoms regardless of whether or not they are receiving concurrent anti-EPS medication at the time of examination. Prediction of side effect risk for the individual patient is not permitted by the strengths of associations reported for grouped data. However, it is suggested that future studies concerned with pharmacological side effect development in humans might benefit from stratification of samples by presence or absence of major and/or minor paroxysmal EEG patterns.

Adolescent↗
PubMed1986

[Synaptic responses of neurons of the red nucleus of the alert cat to stimulation of the sensomotor area of the cortex and the nucleus interpositus of the cerebellum].

Postsynaptic potentials of the red nucleus neurons evoked by stimulation of the cortical sensomotor region and the cerebellar nucleus interpositus were studied in chronic experiments on awake cats by means of intracellules revording. Rubro-spinal neurons identified by their antidromic activation in response to the stimulation. A decrease of the critical depolarization level was a specific feature for mono- and polysynaptic responses of the red nucleus neurons in alert animals. Isolated EPSPs, therefore, were rarely recorded as well as a great number of polysynaptic potentials. Burst discharges of rubro-spinal neurons and intensive activity of the red nucleus interneurons, were observed.

Animals↗