{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T02:05:41Z","timestamp":1778205941418,"version":"3.51.4"},"reference-count":51,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,11,16]],"date-time":"2015-11-16T00:00:00Z","timestamp":1447632000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004488","name":"Hrvatska Zaklada za Znanost","doi-asserted-by":"publisher","award":["IP\u20102014\u201009\u20101501"],"award-info":[{"award-number":["IP\u20102014\u201009\u20101501"]}],"id":[{"id":"10.13039\/501100004488","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Fundamemntal Clinical Pharma"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>New primaquine (<jats:styled-content style=\"fixed-case\">PQ<\/jats:styled-content>) urea and semicarbazide derivatives<jats:bold>1<\/jats:bold>\u2013<jats:bold>4<\/jats:bold>were screened for the first time for central nervous system (<jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content>) and antimalarial activity. Behavioural tests were performed on mice. In vitro cytotoxicity on L\u20106 cells and activity against erythrocytic stages of<jats:italic>Plasmodium falciparum<\/jats:italic>was determined. Compound<jats:bold>4<\/jats:bold>inhibited \u2018head\u2010twitch\u2019 responses and decreased body temperature of mice, which suggests some involvement of the serotonergic system. Compound<jats:bold>4<\/jats:bold>protected mice against clonic seizures and was superior in the antimalarial test. A hybrid of two<jats:styled-content style=\"fixed-case\">PQ<\/jats:styled-content>urea<jats:bold>2<\/jats:bold>showed a strong antimalarial activity, confirming the previous findings of the high activity of bis(8\u2010aminoquinolines) and other bisantimalarial drugs. All the compounds decreased the locomotor activity of mice, what suggests their weak depressive effects on the<jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content>, while<jats:styled-content style=\"fixed-case\">PQ<\/jats:styled-content>derivatives<jats:bold>1<\/jats:bold>and<jats:bold>2<\/jats:bold>increased amphetamine\u2010induced hyperactivity. None of the compounds impaired coordination, what suggests a lack of their neurotoxicity. All the tested compounds presented an antinociceptive activity in the \u2018writhing\u2019 test. Compounds<jats:bold>3<\/jats:bold>and<jats:bold>4<\/jats:bold>were active in nociceptive tests, and those effects were reversed by naloxone. Compound<jats:bold>4<\/jats:bold>could be a useful lead compound in the development of<jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content>active agents and antimalarials, whereas compound<jats:bold>3<\/jats:bold>may be considered as the most promising lead for new antinociceptive agents.<\/jats:p>","DOI":"10.1111\/fcp.12161","type":"journal-article","created":{"date-parts":[[2015,10,26]],"date-time":"2015-10-26T13:52:48Z","timestamp":1445867568000},"page":"58-69","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Pharmacological effects of primaquine ureas and semicarbazides on the central nervous system in mice and antimalarial activity in vitro"],"prefix":"10.1111","volume":"30","author":[{"given":"Ewa","family":"Kedzierska","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Pharmacodynamics Faculty of Pharmacy with Division of Medical Analytics Medical University of Lublin 20 093 Lublin Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6132-6934","authenticated-orcid":false,"given":"Jolanta","family":"Orzelska","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacodynamics Faculty of Pharmacy with Division of Medical Analytics Medical University of Lublin 20 093 Lublin Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivana","family":"Perkovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry Faculty of Pharmacy and Biochemistry University of Zagreb 10 000 Zagreb Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danijel","family":"Kne\u017eevi\u0107","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry Faculty of Pharmacy and Biochemistry University of Zagreb 10 000 Zagreb Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylwia","family":"Fidecka","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacodynamics Faculty of Pharmacy with Division of Medical Analytics Medical University of Lublin 20 093 Lublin Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcel","family":"Kaiser","sequence":"additional","affiliation":[{"name":"Parasite Chemotherapy Medical Parasitology &amp; Infection Biology Swiss Tropical and Public Health Institute 4051 Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Branka","family":"Zorc","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry Faculty of Pharmacy and Biochemistry University of Zagreb 10 000 Zagreb Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,11,16]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2008.08.011"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2012.03.013"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2009.06.063"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm010252q"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-827X(03)00071-5"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.3109\/14756366.2012.663366"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2014.09.013"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2012.05.037"},{"key":"e_1_2_7_10_1","first-page":"51","article-title":"Synthesis and anticonvulsant activity of some 1\u2010cyclohexylidine\/cycloheptylidine\u20104\u2010substituted semicarbazide derivatives","volume":"1","author":"Jain A.","year":"2012","journal-title":"Int. J. Pharmacol. Pharm. Tech."},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2009.05.008"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2012.03.068"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1248\/cpb.55.796"},{"key":"e_1_2_7_14_1","first-page":"1","article-title":"Synthesis, central nervous system activity and structure\u2010activity relationship of N\u2010substituted derivatives of 1\u2010arylimidazolidyn\u20102\u2010ylideneurea and products of their cyclization","volume":"11","author":"Szacon E.","year":"2015","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules19044745"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-540-70995-4"},{"key":"e_1_2_7_17_1","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0022-3565(25)03549-9","article-title":"Simplified method of evaluating dose effect experiments","volume":"96","author":"Litchfield L.T.","year":"1949","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_2_7_18_1","volume-title":"Basic & clinical pharmacology","author":"Katzung B.G.","year":"2012"},{"key":"e_1_2_7_19_1","first-page":"36","volume-title":"Animal and clinical techniques in drug evaluation","author":"Irwin S.","year":"1964"},{"key":"e_1_2_7_20_1","first-page":"412","article-title":"Acetic acid for analgesic screening","volume":"18","author":"Koster R.","year":"1959","journal-title":"Fed. Proc."},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1472-8206.2012.01068.x"},{"key":"e_1_2_7_22_1","first-page":"434","article-title":"Analgesimetry and ranking of analgesic drugs by the receptacle method","volume":"122","author":"Ben\u2010Bassat J.","year":"1959","journal-title":"Arch. Int. Pharmacodyn. Ther."},{"key":"e_1_2_7_23_1","first-page":"27","article-title":"Role of nitric oxide in benzodiazepines\u2010induced antinociception in mice","volume":"54","author":"Talarek S.","year":"2002","journal-title":"Pol. J. Pharmacol."},{"key":"e_1_2_7_24_1","first-page":"305","article-title":"Zur pharmakologischen Charakterisierung des Schalafmittelsdoriden","volume":"85","author":"Gross F.","year":"1955","journal-title":"Schweiz. Med. Wochschr."},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1159\/000134913"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/fcp.12023"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1963.tb01302.x"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.16.6.710"},{"key":"e_1_2_7_29_1","first-page":"50","article-title":"Chloroquine sensitivity of isolates of Plasmodium falciparum adapted to in vitro culture","volume":"33","author":"Ponnudurai T.","year":"1981","journal-title":"Trop. Geogr. Med."},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-442704-4.50021-9"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/0001-706X(93)90083-N"},{"key":"e_1_2_7_32_1","first-page":"473","article-title":"A new fluorimetric assay for cytotoxicity measurements in vitro","volume":"3","author":"Page C.","year":"1993","journal-title":"Int. J. Oncol."},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(94)90396-4"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2010.11.036"},{"key":"e_1_2_7_35_1","volume-title":"Handbook of toxicology","author":"Derelanko M.J.","year":"2002"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00401509"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/0028-3908(83)90215-0"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7221567"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(90)94066-7"},{"key":"e_1_2_7_40_1","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1016\/S0022-3565(25)10813-6","article-title":"Behavioral evidence for differential adaptation of the serotonergic system after acute and chronic treatment with (+\/\u2212)\u20101\u2010(2,5\u2010dimethoxy\u20104\u2010iodophenyl)\u20102\u2010aminopropane (DOI) or ketanserin","volume":"262","author":"Darmani N.A.","year":"1992","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/0091-3057(90)90098-3"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-003-1741-2"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00180832"},{"key":"e_1_2_7_44_1","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/S0022-3565(25)21483-5","article-title":"Differential actions of serotonin antagonists on two behavioral models of serotonin receptor activation in the rat","volume":"228","author":"Lucki I.","year":"1984","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00498511"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pa.17.040177.002013"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/0091-3057(94)00366-Q"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0028-3908(96)00043-3"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0707646105"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/0741-8329(95)00019-N"},{"key":"e_1_2_7_51_1","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/S0031-6997(24)01514-X","article-title":"Animal models of nociception","volume":"53","author":"Le Bars D.","year":"2001","journal-title":"Pharmacol. Rev."},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/fcp.12034"}],"container-title":["Fundamental &amp; Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Ffcp.12161","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/fcp.12161","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,31]],"date-time":"2025-05-31T04:25:41Z","timestamp":1748665541000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/fcp.12161"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,11,16]]},"references-count":51,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2016,2]]}},"alternative-id":["10.1111\/fcp.12161"],"URL":"https:\/\/doi.org\/10.1111\/fcp.12161","archive":["Portico"],"relation":{},"ISSN":["0767-3981","1472-8206"],"issn-type":[{"value":"0767-3981","type":"print"},{"value":"1472-8206","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,11,16]]},"assertion":[{"value":"2015-07-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-10-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-11-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}