Kazumasa Shiozaki | Search PubMed

PubMed2006

Perospirone in treatment of Huntington's disease: a first case report.

Huntington's disease (HD) is a hereditary disorder clinically characterized by involuntary movements, cognitive decline and psychiatric symptoms. We report on a patient with HD, whose involuntary movements and psychiatric symptoms were clinically improved with perospirone, a second-generation antipsychotic agent with antagonistic effects on serotonin 5-HT(2A) and dopamine D(2) (D(2)) receptors, as well as a unique agonistic effect on serotonin 5-HT(1A) (5-HT(1A)) receptors. The fact that perospirone antagonizes D(2) receptors could explain its effects on the hyperkinetic syndrome, while its agonistic effects on 5-HT(1A) receptors may explain the amelioration of psychiatric symptoms (fear and anxiety) in this patient. Future studies would be valuable to elucidate the utility of perospirone for the treatment of involuntary movements and psychiatric symptoms in HD.

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PubMed2004

Decrease in GTP-sensitive high affinity agonist binding of muscarinic acetylcholine receptors in autopsied brains of dementia with Lewy bodies and Alzheimer's disease.

To determine changes in signal transduction from the muscarinic acetylcholine receptor (mAChR) to G protein in brain tissue of dementia with Lewy bodies (DLB) and Alzheimer's disease (AD), we investigated GTP-sensitive agonist high affinity binding, which is considered an index of the formation of the mAChR-G protein complex. Brain tissue was obtained at necropsy from eight patients with DLB, nine patients with Alzheimer's disease and seven patients as controls. Membrane fractions were prepared from frontal and temporal cerebral tissues. Displacement curves of [(3)H]l-quinuclidinyl benzilate (QNB) binding by carbamylcholine were analyzed by the nonlinear least-squares methods. The proportion of and affinity for the agonist in GTP-sensitive agonist high affinity binding were estimated. The percentages GTP-sensitive agonist high affinity bindings were significantly decreased in DLB (P<0.01) and Alzheimer's disease (P<0.05) only in the frontal lobe. There were no significant differences in the temporal lobe. The ratio of agonist affinity (Kd value of low affinity component/Kd value of high affinity component) did not significantly differ among groups in either the frontal lobe or temporal lobe. The concentration of mAChR-G protein complex is considered reduced in the frontal lobe of brains with DLB and Alzheimer's disease. Therefore, signal transduction from mAChR to G protein was disturbed in the frontal lobe in these diseases.

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