A COMPARATIVE STUDY OF DIHYDROXYLATED PHENOTHIAZINE DERIVATIVES AS MITOCHONDRIAL INHIBITORS
— —The effects of several dihydroxylated phenothiazine derivatives on brain mitochondrial calcium retention, respiration and ATP synthesis were studied and compared to those of 7,8‐dihydroxy‐chlorpromazine. This compound has previously been shown to disrupt retention of calcium accumulated in the pr...
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| Veröffentlicht in: | Journal of neurochemistry 1977-08, Vol.29 (2), p.245-249 |
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| container_end_page | 249 |
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| container_issue | 2 |
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| container_title | Journal of neurochemistry |
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| creator | Tjioe, Sarah A. Manian, A. A. O'neill, J. J. |
| description | — —The effects of several dihydroxylated phenothiazine derivatives on brain mitochondrial calcium retention, respiration and ATP synthesis were studied and compared to those of 7,8‐dihydroxy‐chlorpromazine. This compound has previously been shown to disrupt retention of calcium accumulated in the presence of ATP, to inhibit state III and state IV respiration with glutamate as substrate and to inhibit ATP synthesis. It was found that 2,3‐dihydroxypromazine has little effect on mitochondrial calcium retention, but is a potent inhibitor of oxidative phosphorylation. 3,7‐Dihydroxychlorpromazine and 3,8‐dihydroxychlorpromazine produced a relatively slow and incomplete efflux of pre‐accumulated calcium and caused a limited inhibition of respiration. 7,8‐Dihydroxyperphenazine and 7,8‐dihydroxyprochlorperazine promoted an efflux of mitochondrial calcium and inhibited mitochondrial respiration as was seen with 7,8‐dihydroxychlorpromazine. The effects seen with 7,8‐dioxochlorpromazine are also similar to those seen with 7,8‐dihydroxychlorpromazine, suggesting that oxidation products may contribute to the inhibitory effects observed. |
| doi_str_mv | 10.1111/j.1471-4159.1977.tb09615.x |
| format | Article |
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It was found that 2,3‐dihydroxypromazine has little effect on mitochondrial calcium retention, but is a potent inhibitor of oxidative phosphorylation. 3,7‐Dihydroxychlorpromazine and 3,8‐dihydroxychlorpromazine produced a relatively slow and incomplete efflux of pre‐accumulated calcium and caused a limited inhibition of respiration. 7,8‐Dihydroxyperphenazine and 7,8‐dihydroxyprochlorperazine promoted an efflux of mitochondrial calcium and inhibited mitochondrial respiration as was seen with 7,8‐dihydroxychlorpromazine. 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A.</creatorcontrib><creatorcontrib>O'neill, J. J.</creatorcontrib><title>A COMPARATIVE STUDY OF DIHYDROXYLATED PHENOTHIAZINE DERIVATIVES AS MITOCHONDRIAL INHIBITORS</title><title>Journal of neurochemistry</title><addtitle>J Neurochem</addtitle><description>— —The effects of several dihydroxylated phenothiazine derivatives on brain mitochondrial calcium retention, respiration and ATP synthesis were studied and compared to those of 7,8‐dihydroxy‐chlorpromazine. This compound has previously been shown to disrupt retention of calcium accumulated in the presence of ATP, to inhibit state III and state IV respiration with glutamate as substrate and to inhibit ATP synthesis. It was found that 2,3‐dihydroxypromazine has little effect on mitochondrial calcium retention, but is a potent inhibitor of oxidative phosphorylation. 3,7‐Dihydroxychlorpromazine and 3,8‐dihydroxychlorpromazine produced a relatively slow and incomplete efflux of pre‐accumulated calcium and caused a limited inhibition of respiration. 7,8‐Dihydroxyperphenazine and 7,8‐dihydroxyprochlorperazine promoted an efflux of mitochondrial calcium and inhibited mitochondrial respiration as was seen with 7,8‐dihydroxychlorpromazine. The effects seen with 7,8‐dioxochlorpromazine are also similar to those seen with 7,8‐dihydroxychlorpromazine, suggesting that oxidation products may contribute to the inhibitory effects observed.</description><subject>Adenosine Triphosphate - biosynthesis</subject><subject>Animals</subject><subject>Brain - drug effects</subject><subject>Brain - metabolism</subject><subject>Calcium - metabolism</subject><subject>Mitochondria - drug effects</subject><subject>Mitochondria - metabolism</subject><subject>Oxygen Consumption - drug effects</subject><subject>Phenothiazines - pharmacology</subject><subject>Rats</subject><subject>Structure-Activity Relationship</subject><issn>0022-3042</issn><issn>1471-4159</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1977</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqVkMtOwkAUhifGG6Jv4GLiwl3r3HpzYVLbYsdAS0oxootJOx0SSBFsIcLbWyxh79mc5PyXk3wA3GGk42Ye5jpmFtYYNhwdO5alr3PkmNjQtyegc5ROQQchQjSKGLkEV3U9RwibzMQX4Ny2TUpRB3y60IsHQzdxU_4WwFE69icw7kGfhxM_id8nfTcNfDgMgyhOQ-5-8CiAfpDwt7_ACLojOOBp7IVx5Cfc7UMehfy5uSSja3A2zcpa3Rx2F4x7QeqFWj9-4Z7b1yQ1bUNjRUHzPHfUVCqJkKKSFLnBpG0xalmUKoaUkmaR5YWTMUUtUxLLpEZRYKKMKaFdcN_2rqrl90bVa7GY1VKVZfallpta2AxRTDBujI-tUVbLuq7UVKyq2SKrdgIjsQcr5mJPT-zpiT1YcQArtk349vBlky9UcYy2JBv5qZV_ZqXa_aNYvEYeYQb9BSdIgXA</recordid><startdate>197708</startdate><enddate>197708</enddate><creator>Tjioe, Sarah A.</creator><creator>Manian, A. 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J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3685-4dd3bbb9efcec00e3c2db54c87437733e40eec6dabd9a4e376c27635dd12e5f23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1977</creationdate><topic>Adenosine Triphosphate - biosynthesis</topic><topic>Animals</topic><topic>Brain - drug effects</topic><topic>Brain - metabolism</topic><topic>Calcium - metabolism</topic><topic>Mitochondria - drug effects</topic><topic>Mitochondria - metabolism</topic><topic>Oxygen Consumption - drug effects</topic><topic>Phenothiazines - pharmacology</topic><topic>Rats</topic><topic>Structure-Activity Relationship</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tjioe, Sarah A.</creatorcontrib><creatorcontrib>Manian, A. A.</creatorcontrib><creatorcontrib>O'neill, J. J.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of neurochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tjioe, Sarah A.</au><au>Manian, A. A.</au><au>O'neill, J. J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A COMPARATIVE STUDY OF DIHYDROXYLATED PHENOTHIAZINE DERIVATIVES AS MITOCHONDRIAL INHIBITORS</atitle><jtitle>Journal of neurochemistry</jtitle><addtitle>J Neurochem</addtitle><date>1977-08</date><risdate>1977</risdate><volume>29</volume><issue>2</issue><spage>245</spage><epage>249</epage><pages>245-249</pages><issn>0022-3042</issn><eissn>1471-4159</eissn><abstract>— —The effects of several dihydroxylated phenothiazine derivatives on brain mitochondrial calcium retention, respiration and ATP synthesis were studied and compared to those of 7,8‐dihydroxy‐chlorpromazine. This compound has previously been shown to disrupt retention of calcium accumulated in the presence of ATP, to inhibit state III and state IV respiration with glutamate as substrate and to inhibit ATP synthesis. It was found that 2,3‐dihydroxypromazine has little effect on mitochondrial calcium retention, but is a potent inhibitor of oxidative phosphorylation. 3,7‐Dihydroxychlorpromazine and 3,8‐dihydroxychlorpromazine produced a relatively slow and incomplete efflux of pre‐accumulated calcium and caused a limited inhibition of respiration. 7,8‐Dihydroxyperphenazine and 7,8‐dihydroxyprochlorperazine promoted an efflux of mitochondrial calcium and inhibited mitochondrial respiration as was seen with 7,8‐dihydroxychlorpromazine. The effects seen with 7,8‐dioxochlorpromazine are also similar to those seen with 7,8‐dihydroxychlorpromazine, suggesting that oxidation products may contribute to the inhibitory effects observed.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>886330</pmid><doi>10.1111/j.1471-4159.1977.tb09615.x</doi><tpages>5</tpages></addata></record> |
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| ispartof | Journal of neurochemistry, 1977-08, Vol.29 (2), p.245-249 |
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| language | eng |
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| source | MEDLINE; Wiley Online Library All Journals |
| subjects | Adenosine Triphosphate - biosynthesis Animals Brain - drug effects Brain - metabolism Calcium - metabolism Mitochondria - drug effects Mitochondria - metabolism Oxygen Consumption - drug effects Phenothiazines - pharmacology Rats Structure-Activity Relationship |
| title | A COMPARATIVE STUDY OF DIHYDROXYLATED PHENOTHIAZINE DERIVATIVES AS MITOCHONDRIAL INHIBITORS |
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