{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T02:55:32Z","timestamp":1790996132668,"version":"4.1.0"},"reference-count":48,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T00:00:00Z","timestamp":1693180800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund","award":["TKP2021-EGA-25"],"award-info":[{"award-number":["TKP2021-EGA-25"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Selegiline and rasagiline are two selective monoamine oxidase B (MAO-B) inhibitors used in the treatment of Parkinson\u2019s disease. In their clinical application, however, differences in L-dopa-sparing potencies have been observed. The aim of this study was to find neurochemical and behavioral explanations for the antiparkinsonian effects of these drugs. We found that selegiline possesses a dopaminergic enhancer effect: it stimulated the electrically induced [3H]dopamine release without influencing the resting [3H]dopamine release from rat striatal slices in 10\u221210\u201310\u22129 mol\/L concentrations. Rasagiline added in 10\u221213 to 10\u22125 mol\/L concentrations did not alter the resting or electrically stimulated [3H]dopamine release. Rasagiline (10\u22129 mol\/L), however, suspended the stimulatory effect of selegiline on the electrically induced [3H]dopamine release. The trace amine-associated receptor 1 (TAAR1) antagonist EPPTB (10\u22128\u201310\u22127 mol\/L) also inhibited the stimulatory effect of selegiline on [3H]dopamine release. The effect of selegiline in its enhancer dose (5.33 nmol\/kg) against tetrabenazine-induced learning deficit measured in a shuttle box apparatus was abolished by a 5.84 nmol\/kg dose of rasagiline. The selegiline metabolite (\u2212)methamphetamine (10\u22129 mol\/L) also exhibited enhancer activity on [3H]dopamine release. We have concluded that selegiline acts as an MAO-B inhibitor and a dopaminergic enhancer drug, and the latter relates to an agonist effect on TAAR1. In contrast, rasagiline is devoid of enhancer activity but may act as an antagonist on TAAR1.<\/jats:p>","DOI":"10.3390\/ijms241713334","type":"journal-article","created":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T05:46:47Z","timestamp":1693201607000},"page":"13334","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Striking Neurochemical and Behavioral Differences in the Mode of Action of Selegiline and Rasagiline"],"prefix":"10.3390","volume":"24","author":[{"suffix":"Jr.","given":"Laszlo G.","family":"Harsing","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Semmelweis University, Nagyvarad ter 4, 1089 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Timar","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Semmelweis University, Nagyvarad ter 4, 1089 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ildiko","family":"Miklya","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Semmelweis University, Nagyvarad ter 4, 1089 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,28]]},"reference":[{"key":"ref_1","first-page":"393","article-title":"Some puzzling effects of monoamine oxidase inhibitors","volume":"5","author":"Knoll","year":"1972","journal-title":"Adv. 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