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PubMedDate not supplied

Neuronal basis of neuroleptic-induced extrapyramidal side effects.

The article reviews presently commonly accepted concepts of neuronal basis of neuroleptic-induced extrapyramidal side effects. The data obtained both, in humans and laboratory animals, point to the blockade of a large number of the striatal dopamine D2 receptors by neuroleptics as a primary cause of these disturbances. This phenomenon leads to the appearance of parkinsonian symptoms shortly after therapy commencement. On the other hand, chronic administration of neuroleptics evokes supersensitivity to dopamine connected with the increased number of D2 receptors and supersensitivity of D1 receptors, which can be significant for the development of tardive dyskinesia. Primary and secondary changes in the function of dopamine receptors lead to partially opposite, pathological changes in the activity of neuronal pathways connecting the basal ganglia. Besides functional changes, neuroleptic-induced lesions of the striatal neurons and genetic predispositions can also play a role in tardive dyskinesia.

Afferent Pathways↗
PubMed1976

[Huntington's chorea and cerebellar atrophy. Apropos of amanatomo-clinical case].

The authors report the clinical and pathological findings in a 46 years old woman with Huntington's chorea and cerebello-olivar atrophy. Eight previously reported cerebellar atrophies in Huntington's chorea with pathological examination are reviewed. The primary or secondary nature of the cerebellar lesions is discussed.

Adult↗
PubMedDate not supplied

[Features and mechanisms of realization the respiratory influences of the extrapyramydal system structures].

In the publication the modern condition of the problem of suprabulbar regulation of breathing is analysed. The review on structure, neurochemistry and anatomic connections of the red nucleus and substantia nigra with the medullary respiratory center is submitted. The data on the respiratory effects of GABA and apomorphine microinjected into the red nucleus and substantia nigra as well as effects of their electrostimulation after the blockade of GABA and dopamine receptors in the respiratory center are discussed. The conceptual scheme of the mechanisms of realization the respiratory influences of the extrapyramydal system is offered.

Apomorphine↗
PubMed1978

[Choreic dyskinesia and GABA - pharmaco-clinical approach. Preliminary note].

The effects of Baclofen, a gabamimetic drug, have been studied in 4 patients affected by Huntington's Chorea. The biochemical bases of Chorea are discussed in relation to the HVA modifications in the cerebrospinal fluid induced by the drug. Some interesting data on the extrapyramidal physiology may be achieved with further investigations in a greater group of patients.

Adult↗
PubMed1992

Functions of dopamine in the extrapyramidal and limbic systems. Clues for the mechanism of drug actions.

Dopamine (DA) is a neurotransmitter which modulates the transfer of information along fast-conducting pathways at the level of two main nodal points: the ventral striatum, composed by limbic areas (nucleus accumbens, tuberculum olfactorium) and the dorsal striatum, composed by extrapyramidal nuclei (caudate-putamen). These two subdivisions of the enlarged basal ganglia, are provided with different functions; accordingly, limbic DA plays an active role in goal-oriented (motivated) behaviour; instead, extrapyramidal DA is essential for execution of learned motor programs and its impairment results in the symptoms of Parkinson's disease. Various centrally acting drugs are able to interfere with DA transmission or with other neurotransmitter systems which interact with DA. Drugs of abuse owe their incentive properties to a preferential stimulation of DA transmission at the level of the limbic dopaminergic areas. On the other hand, drugs able to block glutamatergic transmission on NMDA receptors are able to selectively potentiate the action of DA at the level of a specific type of DA-receptors, the D-1 type. Knowledge of the role of DA in the brain can provide the basis not only for understanding the mechanism of drug action but also for developing new strategies for the treatment of drug abuse and extrapyramidal disorders.

Animals↗
PubMedDate not supplied

[The role of protein conformational disturbances in the pathomechanism of the extrapyramidal system diseases].

Neurodegenerative disorders are characterised by cell damage due to accumulation of toxic, pathologic proteins. Mutations in genes coding different cell proteins result in conformational disturbances of the protein structure, their accumulation and aggregation manifested at the level of light microscope as various intracellular inclusions. This paper is an attempt of approach to cellular mechanisms underlying neurodegenerative diseases of the extrapyramidal system with special attention to ubiquitin-proteasome pathway -- the pathway whose discoverers received the 2004 Nobel Prize in chemistry.

Animals↗
PubMed1990

Effects of cocaine on extrapyramidal and limbic dynorphin systems.

The principal central nervous system effects of cocaine are a consequence of its ability to inhibit monoaminergic uptake systems. This agent influences dopamine-related behavior in a manner similar to other sympathomimetics, such as methamphetamine; however, the effect of these two agents on neurochemical dopaminergic parameters are distinct. Several peptidergic neurotransmitter systems, such as the dynorphin pathways, have been shown to be distal to and regulated by the postsynaptic activity of dopaminergic pathways; therefore, we evaluated the response of extrapyramidal and limbic dynorphin A1-17 (Dyn) systems to cocaine by measuring Dyn content in associated structures. Extrapyramidal and limbic dynorphin-like immunoreactivity (DLI) content markedly increased after cocaine treatment. This change appeared to be due primarily to the ability of cocaine to block dopamine re-uptake; consequently, the increase in DLI levels was either totally or partially blocked by coadministration of selective D1 (SCH 23390) and D2 (sulpiride) receptor blockers and multiple doses of the selective dopamine uptake blockers, amfonelic acid and GBR 12909, caused cocaine-like enhancement of extrapyramidal DLI content. Serotonin did not appear to play a major role in mediating the cocaine effects on Dyn systems as multiple doses of the selective serotonin uptake blocker, fluoxetine, did not alter extrapyramidal DLI levels, and depletion of serotonin by pretreatment with parachloroamphetamine did not significantly alter the increases in extrapyramidal Dyn content caused by cocaine administration. Because the behavioral effects of cocaine and methamphetamine are similar, the neurochemical response of Dyn systems to both of these agents is compared and discussed.

Animals↗