{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T16:35:44Z","timestamp":1774542944846,"version":"3.50.1"},"reference-count":28,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2020,12,4]],"date-time":"2020-12-04T00:00:00Z","timestamp":1607040000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Membrane phospholipase D (PLD) is associated with numerous neuronal functions, such as axonal growth, synaptogenesis, formation of secretory vesicles, neurodegeneration, and apoptosis. PLD acts mainly on phosphatidylcholine, from which phosphatidic acid (PA) and choline are formed. In turn, PA is a key element of the PLD-dependent secondary messenger system. Changes in PLD activity are associated with the mechanism of action of olanzapine, an atypical antipsychotic. The aim of the present study was to assess the effect of short-term administration of the first-generation antipsychotic drugs haloperidol, chlorpromazine, and fluphenazine on membrane PLD activity in the rat brain. Animals were sacrificed for a time equal to the half-life of the antipsychotic drug in the brain, then the membranes in which PLD activity was determined were isolated from the tissue. The results indicate that only haloperidol in a higher dose increases the activity of phospholipase D. Such a mechanism of action of haloperidol has not been described previously. Induction of PLD activity by haloperidol may be related to its mechanism of cytotoxicity. The finding could justify the use of PLD inhibitors as protective drugs against the cytotoxicity of first-generation antipsychotic drugs like haloperidol.<\/jats:p>","DOI":"10.3390\/ijms21239265","type":"journal-article","created":{"date-parts":[[2020,12,4]],"date-time":"2020-12-04T11:59:00Z","timestamp":1607083140000},"page":"9265","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Enhancement in Phospholipase D Activity as a New Proposed Molecular Mechanism of Haloperidol-Induced Neurotoxicity"],"prefix":"10.3390","volume":"21","author":[{"given":"Marek","family":"Krzystanek","sequence":"first","affiliation":[{"name":"Department and Clinic of Psychiatric Rehabilitation, Department of Psychiatry and Psychotherapy, Faculty of Medical Sciences, Medical School of Silesia in Katowice, Zio\u0142owa 45\/47, 40-635 Katowice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4441-3088","authenticated-orcid":false,"given":"Ewa","family":"Krzystanek","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medical Sciences, Medical School of Silesia in Katowice, Medyk\u00f3w 14, 40-772 Katowice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2188-7547","authenticated-orcid":false,"given":"Katarzyna","family":"Ska\u0142acka","sequence":"additional","affiliation":[{"name":"Institute of Psychology, University of Opole, Kopernika 11A Street, 45-040 Opole, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Artur","family":"Pa\u0142asz","sequence":"additional","affiliation":[{"name":"Department of Histology, Faculty of Medical Sciences, Medical School of Silesia in Katowice, Medyk\u00f3w 18, 40-752 Katowice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1016\/0024-3205(91)90031-6","article-title":"Phospholipase D in cell signaling and its relationship to phospholipase C","volume":"48","author":"Shukla","year":"1991","journal-title":"Life Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"9761","DOI":"10.1016\/S0021-9258(19)83581-0","article-title":"Partial purification and properties of a rat brain phospholipase D","volume":"254","author":"Taki","year":"1979","journal-title":"J. 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