{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T06:56:57Z","timestamp":1776322617643,"version":"3.50.1"},"reference-count":48,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:00:00Z","timestamp":1769126400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:00:00Z","timestamp":1769126400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>\n                      Dopamine receptor agonists, particularly targeting the dopamine D\n                      <jats:sub>2L<\/jats:sub>\n                      receptor (D\n                      <jats:sub>2L<\/jats:sub>\n                      R), have been used to treat Parkinson's disease (PD). However, valvular heart disease and somnolence, mainly caused by activating the serotonin 5\u2010HT\n                      <jats:sub>2B<\/jats:sub>\n                      receptor (5\u2010HT\n                      <jats:sub>2B<\/jats:sub>\n                      R) and dopamine D\n                      <jats:sub>3<\/jats:sub>\n                      receptor (D\n                      <jats:sub>3<\/jats:sub>\n                      R), respectively, currently challenge their clinical use. Here, we aimed to develop a novel dopamine receptor agonist with superior therapeutic efficacy for PD, while minimising adverse reactions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      Matsupexole, a novel nonergot dopamine receptor agonist, was evaluated by agonist activity for D\n                      <jats:sub>2L<\/jats:sub>\n                      R and a 6\u2010hydroxydopamine\u2010lesioned male rat PD model. To explore its adverse effects, the agonist activity for other receptors, including 5\u2010HT\n                      <jats:sub>2B<\/jats:sub>\n                      R and D\n                      <jats:sub>3<\/jats:sub>\n                      R, and the resulting porcine heart valve interstitial cell (PHVIC) proliferation and non\u2010rapid eye movement (REM) sleep induction in male rats were evaluated, in comparison with existing dopamine receptor agonists.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      Matsupexole exhibited potent agonist activity for D\n                      <jats:sub>2L<\/jats:sub>\n                      Rs without inducing 5\u2010HT\n                      <jats:sub>2B<\/jats:sub>\n                      R activation or promoting PHVIC proliferation. Matsupexole demonstrated sustained efficacy in the PD model. In contrast, despite its strong D\n                      <jats:sub>2L<\/jats:sub>\n                      R agonist activity, cabergoline, an ergot dopamine receptor agonist, significantly evoked PHVIC proliferation. Reflecting its higher D\n                      <jats:sub>2L<\/jats:sub>\n                      R\/D\n                      <jats:sub>3<\/jats:sub>\n                      R selectivity, matsupexole did not affect non\u2010REM sleep induction. Although pramipexole, a D\n                      <jats:sub>3<\/jats:sub>\n                      R\u2010favouring nonergot agonist, showed efficacy in the rat PD model, its effect was shorter in duration, and it strongly promoted non\u2010REM sleep. The stabilised interaction between Val190\n                      <jats:sup>5.39<\/jats:sup>\n                      in D\n                      <jats:sub>2L<\/jats:sub>\n                      R and matsupexole, but not pramipexole, further supports the higher D\n                      <jats:sub>2L<\/jats:sub>\n                      R\/D\n                      <jats:sub>3<\/jats:sub>\n                      R selectivity of matsupexole.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>Matsupexole is a promising future, potentially best\u2010in\u2010class dopamine receptor agonist for treating PD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70351","type":"journal-article","created":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T06:18:57Z","timestamp":1769235537000},"page":"2518-2532","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Matsupexole: A novel nonergot dopamine receptor agonist with sustained efficacy in a rat model of Parkinson's disease and limited off\u2010target activity"],"prefix":"10.1111","volume":"183","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-1878-6767","authenticated-orcid":false,"given":"Takayuki","family":"Suzuki","sequence":"first","affiliation":[{"name":"Central Research Laboratories Kissei Pharmaceutical Co., Ltd.  Nagano Japan"},{"name":"Department of Disease Model, Research Institute for Radiation Biology and Medicine Hiroshima University  Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fumiki","family":"Oana","sequence":"additional","affiliation":[{"name":"Central Research Laboratories Kissei Pharmaceutical Co., Ltd.  Nagano Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaki","family":"Oota","sequence":"additional","affiliation":[{"name":"Central Research Laboratories Kissei Pharmaceutical Co., Ltd.  Nagano Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuma","family":"Handa","sequence":"additional","affiliation":[{"name":"Central Research Laboratories Kissei Pharmaceutical Co., Ltd.  Nagano Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Osamu","family":"Kaminuma","sequence":"additional","affiliation":[{"name":"Department of Disease Model, Research Institute for Radiation Biology and Medicine Hiroshima University  Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,1,23]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.5.1945"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16177"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/ci050262q"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/377424a0"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1043-9471(05)80049-7"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2023.1183823"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15868"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-199855001-00002"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/114.5.2283"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1039\/c2cp23784a"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(93)90576-9"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.3233\/JPD-240003"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198804073181402"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-2614(99)00874-X"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0014-2999(00)00745-7"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1246\/bcsj.20180150"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0924-977x(97)00054-0"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.107.134296"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15178"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.102.039867"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cplett.2004.08.082"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00214-004-0602-3"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-15-9235-5"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-15-9235-5"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cplett.2008.03.090"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2015-312283"},{"key":"e_1_2_12_28_1","unstructured":"Molecular Operating Environment (MOE). 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