| Project/Area Number |
08671103
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | Saitama Medical School |
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Principal Investigator |
KAZAWA Tetsushi Saitama Medical School, School of Medicine, Associate professor, 医学部, 助教授 (20204373)
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| Co-Investigator(Kenkyū-buntansha) |
MINATOGAWA Yukiko Saitama Medical School, School of Medicine, Assistant professor, 医学部, 助手 (60146272)
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| Project Period (FY) |
1996 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1998: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1997: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
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| Keywords | carbamazepine / adenosine receptor / psychotropic drugs / rat / psychotropic drugs / carbamazepine / Adenosine受容体 / Carbamasepine / アデソラン受容体 / ドパミン受容体 / 抗精神病薬 |
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| Research Abstract |
Clinically, ft is well known that carbamazepine is effective in affective disorder and it is useful drug for neuroleptic-resistant schizophrenia, but it's basic mechanism is not known. Unlike other neurorrptics, carbamazepine has not affinity for dopamine receptor and other monoamine receptors. It has weak affinity for adenosine receptors. Adenosine receptors are classified into two subtypes, A-1 and A-2. A-1 adenosine receptor is negatively linked to adenylate cyclaso and A-2 adenosine receptor is positively linked to adenylate cyclase. Adenosine receptor modulate the release of neurotransmitter in CNS.Behaviorally adonosme receptor relate with the locomotion activity of rodents.
We investigated the affinities of various psychotropic drugs for A-land A-2 adenosine receptors labeled by ^3H-CHA and ^8H-CGS-21680, respectively. Of the neuroleptics, , carbainazepine and clonazepam showed the weak afflnities for A-1 receptor, sodium valproate, haloperidol and chiorpromazine did not show the
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affinity for both A-i and A-2 ade nosine receptors.
In the next step, we investigated the influence of the chronic treatment of some drugs for adenosine receptors in rats. Chronic treatment of carbamazepine (10mg/kg twice a day 2 weeks, p.o.) increased the A-1 receptor density, but did not change the density of A-2 receptors. Concomitant treatment of carbamazepine and haloperidol (1mg/kg) prevented the increase of A-i receptor density by carbamazepine. Chronic treatment of haloporidol slightly decreased the density of A-1 receptor..
It is known that chronic treatment of lithium prevent the increase of dopamine receptor density by chronic treatment of haloperidol. So we investigated whether or not carba.mazepine prevented the increase of D-2 dopamine receptor (labeled by 3H-YM-09151-2) by chronic treatment of haloperidol. Chronic treatment of carbamazepine did not prevent the increase of dopamine receptor density by haloperidol.
These results suggest that adenosine receptors play some role in the antipsychotic effects of carbamazepine. Less
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