{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T09:07:09Z","timestamp":1762160829452,"version":"3.37.3"},"reference-count":16,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2009,3,13]],"date-time":"2009-03-13T00:00:00Z","timestamp":1236902400000},"content-version":"vor","delay-in-days":12370,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Acta Pharmacologica et Toxicologica"],"published-print":{"date-parts":[[1975,5]]},"abstract":"<jats:p><jats:bold>Abstract:<\/jats:bold>The inhibition of the simultaneous uptake of<jats:sup>3<\/jats:sup>H\u2010l\u2010noradrenaline (NA) and<jats:sup>14<\/jats:sup>C\u20105\u2010hydroxytryptamine (5\u2010HT) in slices of the midbrain\u2010hypothalamus region of the rat brain after oral administration of desipramine, imipramine, nortriptyline, amitriptyline, chlordesipramine and chlorimipramine was determined. All compounds were more active in inhibiting the NA uptake than the 5\u2010HT uptake. This difference was very marked for desipramine, imipramine, nortriptyline and chlordesipramine. Chlorimipramine was almost as active on the 5\u2010HT uptake (ED<jats:sub>50<\/jats:sub>= 35 mg\/kg orally) as on the NA uptake (ED<jats:sub>60<\/jats:sub>= 20 mg\/kg orally) and amitriptyline had low activity on both uptake mechanisms (ED<jats:sub>50<\/jats:sub>&gt; 50 mg\/kg orally). Desipramine and imipramine were the most active compounds on the NA uptake (ED<jats:sub>50<\/jats:sub>= 8 mg\/kg orally for both compounds) and the duration of the action was very long. The ED<jats:sub>50<\/jats:sub>values for nortriptyline and chlordesipramine in inhibiting the NA uptake were about 20 mg\/kg orally for both compounds. The inhibition of the 5\u2010HT uptake was less than 50% at 50 mg\/kg orally for all compounds except for imipramine (ED<jats:sub>50<\/jats:sub>= 50 mg\/kg orally) and for chlorimipramine. The role of the biotransformation for the inhibitory activities of imipramine, chlorimipramine and amitriptyline was investigated in animals pre\u2010treated with SKF 525 A. The inhibitory potency of imipramine was increased by the same factor for both uptake mechanisms probably due to the large increase in the concentration of imipramine in the rat brain, which was demonstrated after the administration of<jats:sup>14<\/jats:sup>C\u2010imipramine. The inhibitory activity of chlorimipramine was somewhat more increased for the 5\u2010HT uptake than for the NA uptake. The low activity of amitriptyline seems to be mainly due to poor resorption, since pretreatment of the animals with SKF 525 A only slightly increased the potency whereas intraperitoneal injection of amitriptyline had a rather marked effect on the NA uptake (ED<jats:sub>50<\/jats:sub>= 11 mg\/kg intraperitoneally).<\/jats:p>","DOI":"10.1111\/j.1600-0773.1975.tb00807.x","type":"journal-article","created":{"date-parts":[[2010,7,29]],"date-time":"2010-07-29T14:51:08Z","timestamp":1280415068000},"page":"395-408","source":"Crossref","is-referenced-by-count":69,"title":["Tricyclic Antidepressant Agents. II. Effect of Oral Administration on the Uptake of<sup>3<\/sup>H\u2010Noradrenaline and<sup>14<\/sup>C\u20105\u2010Hydroxytryptamine in Slices of the Midbrain\u2010Hypothalamus Region of the Rat"],"prefix":"10.1111","volume":"36","author":[{"given":"Svante B.","family":"Ross","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna L.","family":"Renyi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,3,13]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042-7158.1970.tb08419.x"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(69)90113-7"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(69)90114-9"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042-7158.1973.tb10645.x"},{"key":"e_1_2_1_6_1","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/S0022-3565(25)26687-3","article-title":"Species differences in the metabolism of imipramine and desmethylimipramine (DMI)","volume":"143","author":"Dingell J. V.","year":"1964","journal-title":"J. Pharmacol. Exp. Therap."},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/2041318a0"},{"key":"e_1_2_1_8_1","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/S0022-3565(25)27359-1","article-title":"Regional studies of catecholamines in the rat brain. IV. Effects of drugs on the disposition and metabolism of 3H\u2010norepinephrine and 3H\u2010dopamine","volume":"153","author":"Glowinski J.","year":"1966","journal-title":"J. Pharmacol. Exp. Therap."},{"issue":"295","key":"e_1_2_1_9_1","first-page":"7","article-title":"Reserpine\u2010resistant uptake of catecholamines in isolated tissues of the rat","volume":"71","author":"Hamberger B.","year":"1967","journal-title":"Acta physiol. scand."},{"key":"e_1_2_1_10_1","first-page":"66","article-title":"Catecholamine uptake by synaptosomes from rat brain. Structure activity relationship of drugs with differential effects on dopamine and norepinephrine neurons","volume":"7","author":"Horn A. S.","year":"1971","journal-title":"Mol. Pharmacol."},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(67)90084-2"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(69)90091-0"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0773.1975.tb00806.x"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(71)90325-0"},{"key":"e_1_2_1_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(72)90276-2"},{"key":"e_1_2_1_16_1","first-page":"45","volume-title":"Symposium on pharmacological agents on biogenic amines in the central nervous system","author":"Ross S. 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Therap."}],"container-title":["Acta Pharmacologica et Toxicologica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1600-0773.1975.tb00807.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1600-0773.1975.tb00807.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,23]],"date-time":"2025-02-23T15:56:42Z","timestamp":1740326202000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1600-0773.1975.tb00807.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1975,5]]},"references-count":16,"journal-issue":{"issue":"5","published-print":{"date-parts":[[1975,5]]}},"alternative-id":["10.1111\/j.1600-0773.1975.tb00807.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1600-0773.1975.tb00807.x","archive":["Portico"],"relation":{},"ISSN":["0001-6683"],"issn-type":[{"type":"print","value":"0001-6683"}],"subject":[],"published":{"date-parts":[[1975,5]]}}}