{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T13:14:04Z","timestamp":1779110044856,"version":"3.51.4"},"reference-count":59,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2019,7,31]],"date-time":"2019-07-31T00:00:00Z","timestamp":1564531200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2019,7,31]],"date-time":"2019-07-31T00:00:00Z","timestamp":1564531200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100014718","name":"Innovative Research Group Project of the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81603106"],"award-info":[{"award-number":["81603106"]}],"id":[{"id":"10.13039\/100014718","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014718","name":"Innovative Research Group Project of the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81703339"],"award-info":[{"award-number":["81703339"]}],"id":[{"id":"10.13039\/100014718","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014718","name":"Innovative Research Group Project of the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U1801287"],"award-info":[{"award-number":["U1801287"]}],"id":[{"id":"10.13039\/100014718","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014718","name":"Innovative Research Group Project of the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["NSFC 81603106"],"award-info":[{"award-number":["NSFC 81603106"]}],"id":[{"id":"10.13039\/100014718","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012156","name":"Shenzen Municipal Technical Project","doi-asserted-by":"publisher","award":["JCYJ20160331141459373"],"award-info":[{"award-number":["JCYJ20160331141459373"]}],"id":[{"id":"10.13039\/501100012156","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013076","name":"National Major Science and Technology Projects of China","doi-asserted-by":"publisher","award":["2018ZX09301031\u2010002"],"award-info":[{"award-number":["2018ZX09301031\u2010002"]}],"id":[{"id":"10.13039\/501100013076","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Cerebral vasospasm and neuronal apoptosis after subarachnoid haemorrhage (SAH) is the major cause of morbidity and mortality in SAH patients. So far, single\u2010target agents have not prevented its occurrence. Memantine, a non\u2010competitive NMDA re3ceptor antagonist, is known to alleviate brain injury and vasospasm in experimental models of SAH. Impairment of NO availability also contributes to vasospasm. Recently, we designed and synthesized a memantine nitrate MN\u201008, which has potent dual functions: neuroprotection and vasodilation. Here, we have tested the therapeutic effects of MN\u201008 in animal models of SAH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>Binding to NMDA receptors (expressed in HEK293 cells), NO release and vasodilator effects of MN\u201008 were assessed in vitro. Therapeutic effects of MN\u201008 were investigated in vivo, using rat and rabbit SAH models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>MN\u201008 bound to the NMDA receptor, slowly releasing NO in vitro and in vivo. Consequently, MN\u201008 relaxed the pre\u2010contracted middle cerebral artery ex vivo and increased blood flow velocity in small vessels of the mouse cerebral cortex. It did not, however, lower systemic blood pressure. In an endovascular perforation rat model of SAH, MN\u201008 improved the neurological scores and ameliorated cerebral vasospasm. Moreover, MN\u201008 also alleviated cerebral vasospasm in a cisterna magna single\u2010injection model in rabbits. MN\u201008 attenuated neural cell apoptosis in both rat and rabbit models of SAH. Importantly, the therapeutic benefit of MN\u201008 was greater than that of memantine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>MN\u201008 has neuroprotective potential and can ameliorate vasospasm in experimental SAH models.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.14763","type":"journal-article","created":{"date-parts":[[2019,6,10]],"date-time":"2019-06-10T10:39:12Z","timestamp":1560163152000},"page":"3318-3335","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["The dual\u2010functional memantine nitrate MN\u201008 alleviates cerebral vasospasm and brain injury in experimental subarachnoid haemorrhage models"],"prefix":"10.1111","volume":"176","author":[{"given":"Fangcheng","family":"Luo","sequence":"first","affiliation":[{"name":"Institute of New Drug Research and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio\u2010cerebrovascular Diseases Jinan University College of Pharmacy  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liangmiao","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of New Drug Research and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio\u2010cerebrovascular Diseases Jinan University College of Pharmacy  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhixiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of New Drug Research and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio\u2010cerebrovascular Diseases Jinan University College of Pharmacy  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zeyu","family":"Zhu","sequence":"additional","affiliation":[{"name":"Institute of New Drug Research and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio\u2010cerebrovascular Diseases Jinan University College of Pharmacy  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zheng","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of New Drug Research and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio\u2010cerebrovascular Diseases Jinan University College of Pharmacy  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baojian","family":"Guo","sequence":"additional","affiliation":[{"name":"Institute of New Drug Research and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio\u2010cerebrovascular Diseases Jinan University College of Pharmacy  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ning","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of New Drug Research and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio\u2010cerebrovascular Diseases Jinan University College of Pharmacy  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Ju","sequence":"additional","affiliation":[{"name":"School of Chemical Biology and Biotechnology Peking University Shenzhen Graduate School  Shenzhen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiang","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Chemical Biology and Biotechnology Peking University Shenzhen Graduate School  Shenzhen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shupeng","family":"Li","sequence":"additional","affiliation":[{"name":"School of Chemical Biology and Biotechnology Peking University Shenzhen Graduate School  Shenzhen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xifei","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Modern Toxicology of Shenzhen Center for Disease Control and Prevention  Shenzhen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinghung","family":"Mak","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation) The Hong Kong Polytechnic University Shenzhen Research Institute  Shenzhen China"},{"name":"Department of Applied Biology and Chemical Technology, Institute of Modern Chinese Medicine The Hong Kong Polytechnic University  Hung Hom Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yifan","family":"Han","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation) The Hong Kong Polytechnic University Shenzhen Research Institute  Shenzhen China"},{"name":"Department of Applied Biology and Chemical Technology, Institute of Modern Chinese Medicine The Hong Kong Polytechnic University  Hung Hom Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yewei","family":"Sun","sequence":"additional","affiliation":[{"name":"Institute of New Drug Research and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio\u2010cerebrovascular Diseases Jinan University College of Pharmacy  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuqiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of New Drug Research and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio\u2010cerebrovascular Diseases Jinan University College of Pharmacy  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gaoxiao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of New Drug Research and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio\u2010cerebrovascular Diseases Jinan University College of Pharmacy  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0690-1673","authenticated-orcid":false,"given":"Zaijun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of New Drug Research and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio\u2010cerebrovascular Diseases Jinan University College of Pharmacy  Guangzhou China"},{"name":"International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE) Jinan University College of Pharmacy  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,7,31]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13877"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13879"},{"issue":"2","key":"e_1_2_11_4_1","first-page":"71","article-title":"Cerebral arterial spasm. Part 8: The treatment of delayed cerebral arterial spasm in human beings","volume":"6","author":"Allen G. S.","year":"1976","journal-title":"Surgical Neurology"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0969\u20108051(01)00293\u20101"},{"issue":"6","key":"e_1_2_11_6_1","first-page":"672","article-title":"Therapeutic effect of caspase inhibitors in the prevention of apoptosis and reversal of chronic cerebral vasospasm","volume":"9","author":"Aoki K.","year":"2002","journal-title":"Stroke"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1517\/14728222.2014.983900"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jcbfm.9600283"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12278"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2013.00106"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304\u20103940(87)90505\u20102"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1161\/STR.0b013e3182587839"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14153"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12028\u2010011\u20109605\u20109"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1080\/01616412.1993.11740153"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00701\u2010011\u20101049\u20107"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12975\u2010013\u20100257\u20102"},{"key":"e_1_2_11_18_1","first-page":"e3564","article-title":"Whole animal perfusion fixation for rodents","volume":"65","author":"Gage G. J.","year":"2012","journal-title":"Journal of Visualized Experiments"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.26.4.627"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1121"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20103\u20107091\u20100353\u20101_8"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2005.22.3"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms160614171"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035\u2010014\u20108767\u20109"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1177\/1087057116628437"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1161\/hs0202.103410"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn936"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1227\/00006123-200107000-00005"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.00872.x"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742\u20102094\u201011\u20102"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcp1605827"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1385\/NCC:4:1:068"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1039\/C6MD00509H"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2013.246"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(16)30668\u20107"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.22.8.971"},{"key":"e_1_2_11_37_1","article-title":"One\u2010channel cell\u2010attached patch\u2010clamp recording","volume":"88","author":"Maki B. A.","year":"2014","journal-title":"Journal of Visualized Experiments"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12955"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12975\u2010016\u20100466\u20106"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(98)00133-X"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2013.173"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20103\u2010211\u201075718\u20105_28"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1179\/174313209X393564"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000038108.71560.70"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2013.49"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1099\u20101344(199703)39:3<241::AID\u2010JLCR966>3.0.CO;2\u2010V"},{"issue":"1","key":"e_1_2_11_47_1","first-page":"208","article-title":"Decreased nitric oxide availability contributes to acute cerebral ischemia after subarachnoid hemorrhage","volume":"47","author":"Schwartz A. Y.","year":"2000","journal-title":"Neurosurgery"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1227\/01.NEU.0000134557.82423.B2"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035\u2010010\u20108155\u2010z"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004647\u2010200003000\u201000018"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2011.196"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/972417"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2007.08.004"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncpcardio0046"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X15605848"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1179\/174313209X382412"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1177\/1073858406296259"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1227\/NEU.0b013e3181fe23c1"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2017.00611"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1021\/jf301511m"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbph.14763","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.14763","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bph.14763","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.14763","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T12:38:06Z","timestamp":1779107886000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.14763"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,31]]},"references-count":59,"journal-issue":{"issue":"17","published-print":{"date-parts":[[2019,9]]}},"alternative-id":["10.1111\/bph.14763"],"URL":"https:\/\/doi.org\/10.1111\/bph.14763","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,31]]},"assertion":[{"value":"2018-10-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-06-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-07-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}