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OtherReview Article

Functional Pharmacology in Human Brain

Maurizio Raiteri
Pharmacological Reviews June 2006, 58 (2) 162-193; DOI: https://doi.org/10.1124/pr.58.2.5
Maurizio Raiteri
Dipartimento di Medicina Sperimentale, Sezione di Farmacologia e Tossicologia and Centro di Eccellenza per la Ricerca Biomedica, Università di Genova, Genoa, Italy
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Abstract

Most neurological and psychiatric disorders involve selective or preferential impairments of neurotransmitter systems. Therefore, studies of functional transmitter pathophysiology in human brain are of unique importance in view of the development of effective, mechanism-based, therapeutic modalities. It is well known that central nervous system functional proteins, including receptors, transporters, ion channels, and enzymes, can exhibit high heterogeneity in terms of structure, function, and pharmacological profile. If the existence of types and subtypes of functional proteins amplifies the possibility of developing selective drugs, such heterogeneity certainly increases the likelihood of interspecies differences. It is therefore essential, before choosing animal models to be used in preclinical pharmacology experimentation, to establish whether functionally corresponding proteins in men and animals also display identical pharmacological profiles. Because of evidence that scaffolding proteins, trafficking between plasma membrane and intracellular pools, phosphorylation and allosteric modulators can affect the function of receptors and transporters, experiments with human clones expressed in host cells where the environment of native receptors is rarely reproduced should be interpreted with caution. Thus, the use of neurosurgically removed fresh human brain tissue samples in which receptors, transporters, ion channels, and enzymes essentially retain their natural environment represents a unique experimental approach to enlarge our understanding of human brain processes and to help in the choice of appropriate animal models. Using this experimental approach, many human brain functional proteins, in particular transmitter receptors, have been characterized in terms of localization, function, and pharmacological properties.

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Pharmacological Reviews: 58 (2)
Pharmacological Reviews
Vol. 58, Issue 2
1 Jun 2006
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OtherReview Article

Functional Pharmacology in Human Brain

Maurizio Raiteri
Pharmacological Reviews June 1, 2006, 58 (2) 162-193; DOI: https://doi.org/10.1124/pr.58.2.5

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OtherReview Article

Functional Pharmacology in Human Brain

Maurizio Raiteri
Pharmacological Reviews June 1, 2006, 58 (2) 162-193; DOI: https://doi.org/10.1124/pr.58.2.5
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  • Article
    • Abstract
    • I. Introduction
    • II. Cholinergic Receptors
    • III. Adrenergic Receptors
    • IV. Dopamine Receptors and Transporters
    • V. Serotoninergic Receptors
    • VI. GABA Receptors
    • VII. Glutamatergic Receptors
    • VIII. Neuropeptide Receptors
    • IX. Cannabinoids and Cannabinoid Receptors
    • X. Calcium Channels and Intraterminal Calcium Pools
    • XI. Neurotransmitters in the Alzheimer's Brain
    • XII. Epilepsy: In Vitro and in Vivo Studies
    • XIII. Brain Ischemia and Traumatic Injury
    • XIV. Effects of HIV-1 Proteins
    • XV. Parkinson's Disease: In Vivo Microdialysis Studies
    • XVI. Conclusions
    • Acknowledgments
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