{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T03:52:46Z","timestamp":1791172366675,"version":"4.1.0"},"reference-count":75,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2009,1,30]],"date-time":"2009-01-30T00:00:00Z","timestamp":1233273600000},"content-version":"vor","delay-in-days":3348,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[1999,12]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>The treatment of Parkinson's disease relies predominantly upon dopamine replacement therapy, usually with l\u2010dihydroxyphenylalanine (<jats:sc>L<\/jats:sc>\u2010DOPA). However, side\u2010effects of long\u2010term treatment, such as <jats:sc>L<\/jats:sc>\u2010DOPA\u2010induced dyskinesias can be more debilitating than the disease itself. Non\u2010dopaminergic treatment strategies might therefore be advantageous.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The aim of this study was to investigate the potential anti\u2010parkinsonian efficacy of the \u03ba\u2010opioid receptor agonist, enadoline, and the \u03b1\u2010adrenoreceptor agonist, clonidine, both alone or in combination, in the reserpine\u2010treated rat model of Parkinson's disease.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Rats were treated with reserpine (3\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>), and experiments carried out 18\u2003h later, at which time they exhibited profound akinesia (normal animals 1251\u00b1228 mobile counts h<jats:sup>\u22121<\/jats:sup>, reserpine\u2010treated animals 9\u00b12 mobile counts h<jats:sup>\u22121<\/jats:sup>). Both enadoline and clonidine increased locomotion in reserpine\u2010treated rats in a dose\u2010dependent manner. The maximum locomotor\u2010stimulating effect of enadoline alone was seen at a dose of 0.2\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup> (208\u00b163 mobile counts h<jats:sup>\u22121<\/jats:sup>). The maximum effect of clonidine was seen at a dose of 2\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup> (536\u00b1184 mobile counts h<jats:sup>\u22121<\/jats:sup>).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Co\u2010administration of enadoline (0.1\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>) and clonidine (0.01\u20130.1\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>) at sub\u2010threshold doses, synergistically increased locomotion.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The synergistic stimulation of locomotion in the reserpine\u2010treated rat involved activation of \u03ba\u2010opioid receptors and a combination of both \u03b1<jats:sub>1<\/jats:sub> and \u03b1<jats:sub>2<\/jats:sub>\u2010adrenoreceptors.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The results presented suggest a need for further studies on the potential of stimulating \u03ba\u2010opioid and\/or \u03b1\u2010adrenoreceptors as a therapy for Parkinson's disease. Furthermore, the studies may offer potential mechanistic explanations of the ability of \u03b1<jats:sub>2<\/jats:sub>\u2010adrenergic receptor antagonist to reduce <jats:sc>L<\/jats:sc>\u2010DOPA\u2010induced dyskinesia in Parkinson's disease.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (1999) <jats:bold>128<\/jats:bold>, 1577\u20131585; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0702943\">10.1038\/sj.bjp.0702943<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0702943","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T20:28:56Z","timestamp":1106944136000},"page":"1577-1585","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["The adrenergic receptor agonist, clonidine, potentiates the anti\u2010parkinsonian action of the selective \u03ba\u2010opioid receptor agonist, enadoline, in the monoamine\u2010depleted rat"],"prefix":"10.1111","volume":"128","author":[{"given":"M P","family":"Hill","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J M","family":"Brotchie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,30]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(89)90103-0"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00426104"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00429276"},{"key":"e_1_2_7_5_1","first-page":"323","article-title":"Characterization of the alpha\u20102C adrenergic receptor subtype in the opossum kidney and in the OK cell line","volume":"259","author":"BLAXALL H.S.","year":"1991","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.2165\/00023210-199810030-00004"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/00019052-199708000-00010"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.870130603"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6123(08)61342-4"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.870060208"},{"key":"e_1_2_7_11_1","first-page":"1","article-title":"Pharmacological characteristics of alpha 2\u2010adrenergic receptors: comparison of pharmacologically defined subtypes with subtypes identified by molecular cloning","volume":"42","author":"BYLUND D.B.","year":"1992","journal-title":"Mol. Pharmacol."},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01255820"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02263486"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(90)90108-M"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(90)90346-S"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00184286"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02246054"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/0028-3908(87)90110-9"},{"key":"e_1_2_7_19_1","first-page":"1067","article-title":"Opposite effects of mu and kappa opiate agonists on dopamine release in the nucleus accumbens and in the dorsal caudate of freely moving rats","volume":"244","author":"DI CHIARA G.","year":"1988","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0091-3057(76)90107-6"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(76)90308-3"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/0091-3057(76)90217-3"},{"key":"e_1_2_7_23_1","first-page":"413","article-title":"Kappa opioids in rhesus monkeys. I. Diuresis, sedation, analgesia and discriminative stimulus effects","volume":"242","author":"DYKSTRA L.A.","year":"1987","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_2_7_24_1","first-page":"30","article-title":"Nor\u2010binaltorphimine: a potent and selective kappa\u2010opioid receptor antagonist with long\u2010lasting activity in vivo","volume":"316","author":"ENDOH T.","year":"1992","journal-title":"Arch. Int. Pharmacodyn. Ther."},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0773.1990.tb00797.x"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(71)90178-X"},{"key":"e_1_2_7_27_1","first-page":"178","volume-title":"Advances in Parkinsonism","author":"FARLEY I.J.","year":"1976"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(91)90065-X"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(91)90064-W"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1097\/00002826-199108000-00008"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.16.4.213"},{"key":"e_1_2_7_32_1","first-page":"407","article-title":"Pharmacological characterization of rat alpha 2\u2010adrenergic receptors","volume":"40","author":"HARRISON J.K.","year":"1991","journal-title":"Mol. Pharmacol."},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1998.6819"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00238214"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(83)90563-5"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(84)90253-X"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(95)00385-X"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0702523"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.870130206"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1990.tb12110.x"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(96)00407-1"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1994.tb14843.x"},{"key":"e_1_2_7_43_1","doi-asserted-by":"crossref","first-page":"10470","DOI":"10.1016\/S0021-9258(18)99248-3","article-title":"Isolation of rat genomic clones encoding subtypes of the alpha 2\u2010adrenergic receptor. Identification of a unique receptor subtype","volume":"266","author":"LANIER S.M.","year":"1991","journal-title":"J. Biol. Chem."},{"key":"e_1_2_7_44_1","first-page":"89","article-title":"A kappa opioid effect: increased urination in the rat","volume":"224","author":"LEANDER J.D.","year":"1983","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1987.tb11398.x"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.11-06-01565.1991"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02259662"},{"key":"e_1_2_7_48_1","first-page":"241","article-title":"Distribution and pharmacology of alpha 2\u2010adrenoceptors in the central nervous system","volume":"46","author":"MACDONALD E.","year":"1995","journal-title":"J. Physiol. Pharmacol."},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02252623"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(95)00358-W"},{"key":"e_1_2_7_51_1","first-page":"196","article-title":"Rotational behavior mediated by dopaminergic and nondopaminergic mechanisms after intranigral microinjection of specific mu, delta and kappa opioid agonists","volume":"246","author":"MATSUMOTO R.R.","year":"1988","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(88)90914-6"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(93)90116-W"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002130050372"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4684-5347-8_29"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1097\/00008877-199508000-00010"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(85)91074-1"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.2183\/pjab.57.351"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1998.6963"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-6147(96)10022-5"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903280409"},{"key":"e_1_2_7_62_1","first-page":"128","article-title":"Diuretic actions in man of a selective kappa opioid agonist: U\u201062,066E","volume":"240","author":"PETERS G.R.","year":"1987","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(87)90585-6"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/0166-4328(87)90060-X"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00499922"},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1973.00490200055007"},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(90)94124-G"},{"key":"e_1_2_7_68_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1990.tb04963.x"},{"key":"e_1_2_7_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/0091-3057(88)90316-4"},{"key":"e_1_2_7_70_1","doi-asserted-by":"publisher","DOI":"10.1002\/syn.890120303"},{"key":"e_1_2_7_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(85)90074-5"},{"key":"e_1_2_7_72_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00212761"},{"key":"e_1_2_7_73_1","first-page":"23","article-title":"Biochemical, functional and behavioural evaluation of a series of novel antipsychotic\u2010like agents","volume":"266","author":"VON VOIGTLANDER P.F.","year":"1983","journal-title":"Arch. Int. Pharmacodyn. Ther."},{"key":"e_1_2_7_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/0091-3057(82)90226-X"},{"key":"e_1_2_7_75_1","first-page":"653","article-title":"The influence of alpha\u2010adrenergic drugs on catalepsy induced by haloperidol or fluphenazine in rats","volume":"30","author":"WEILOSZ M.","year":"1978","journal-title":"Pol. J. Pharmacol. Pharm."},{"key":"e_1_2_7_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/0169-328X(91)90064-5"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0702943","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0702943","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1038\/sj.bjp.0702943","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,28]],"date-time":"2023-10-28T16:51:43Z","timestamp":1698511903000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1038\/sj.bjp.0702943"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,12]]},"references-count":75,"journal-issue":{"issue":"7","published-print":{"date-parts":[[1999,12]]}},"alternative-id":["10.1038\/sj.bjp.0702943"],"URL":"https:\/\/doi.org\/10.1038\/sj.bjp.0702943","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,12]]},"assertion":[{"value":"2009-01-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}