{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T10:08:19Z","timestamp":1783591699261,"version":"3.55.0"},"reference-count":11,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"4527","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[1981,12,18]]},"abstract":"<jats:p>A dihydropyridine-pyridinium salt type of redox system is used in a general and flexible method for site-specific or sustained delivery (or both) of drugs to the brain. A biologically active compound linked to a lipoidal dihydropyridine carrier easily penetrates the blood-brain barrier. Oxidation of the carrier part in vivo to the ionic pyridinium salt prevents its elimination from the brain, while elimination from the general circulation is accelerated. Subsequent cleavage of the quaternary carrier-drug species results in sustained delivery of the drug in the brain and facile elimination of the carrier part.<\/jats:p>","DOI":"10.1126\/science.7313698","type":"journal-article","created":{"date-parts":[[2006,10,5]],"date-time":"2006-10-05T17:45:58Z","timestamp":1160070358000},"page":"1370-1372","source":"Crossref","is-referenced-by-count":164,"title":["Site-Specific, Sustained Release of Drugs to the Brain"],"prefix":"10.1126","volume":"214","author":[{"given":"Nicholas","family":"Bodor","sequence":"first","affiliation":[{"name":"Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hassan H.","family":"Farag","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"Marcus E.","family":"Brewster","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_2_1_1_1","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1021\/jm00223a017","volume":"19","year":"1976","unstructured":"BODOR, N, IMPROVED DELIVERY THROUGH BIOLOGICAL-MEMBRANES .1. SYNTHESIS AND PROPERTIES OF 1-METHYL-1,6-DIHYDROPYRIDINE-2-CARBALDOXIME, A PRO-DRUG OF N-METHYLPYRIDINIUM-2-CARBALDOXIME CHLORIDE, JOURNAL OF MEDICINAL CHEMISTRY 19: 102 (1976).","journal-title":"JOURNAL OF MEDICINAL CHEMISTRY"},{"key":"e_1_2_1_2_1","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1002\/jps.2600670531","volume":"67","year":"1978","unstructured":"BODOR, N, ELIMINATION OF A QUATERNARY PYRIDINIUM SALT DELIVERED AS ITS DIHYDROPYRIDINE DERIVATIVE FROM BRAIN OF MICE, JOURNAL OF PHARMACEUTICAL SCIENCES 67: 685 (1978).","journal-title":"JOURNAL OF PHARMACEUTICAL SCIENCES"},{"key":"e_1_2_1_3_1","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1126\/science.1166305","volume":"190","year":"1975","unstructured":"BODOR, N, DELIVERY OF A QUATERNARY PYRIDINIUM SALT ACROSS BLOOD-BRAIN-BARRIER BY ITS DIHYDROPYRIDINE DERIVATIVE, SCIENCE 190: 155 (1975).","journal-title":"SCIENCE"},{"key":"e_1_2_1_4_1","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1021\/jm00189a025","volume":"22","year":"1979","unstructured":"CUSHMAN, M, CONFORMATIONS, DNA BINDING PARAMETERS, AND ANTI-LEUKEMIC ACTIVITY OF CERTAIN CYTOTOXIC PROTOBERBERINE ALKALOIDS, JOURNAL OF MEDICINAL CHEMISTRY 22: 331 (1979).","journal-title":"JOURNAL OF MEDICINAL CHEMISTRY"},{"key":"e_1_2_1_5_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1021\/cr60275a001","volume":"72","year":"1972","unstructured":"EISNER, U, CHEMISTRY OF DIHYDROPYRIDINES, CHEMICAL REVIEWS 72: 1 (1972).","journal-title":"CHEMICAL REVIEWS"},{"key":"e_1_2_1_6_1","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1002\/ardp.19102480906","volume":"248","year":"1910","unstructured":"GADAMER, J, ARCH PHARM 248: 670 (1910).","journal-title":"ARCH PHARM"},{"key":"e_1_2_1_7_1","first-page":"321","volume":"67","year":"1976","unstructured":"HOSHI, A, ANTITUMOR ACTIVITY OF BERBERRUBINE DERIVATIVES, GANN 67: 321 (1976).","journal-title":"GANN"},{"key":"e_1_2_1_8_1","first-page":"159","year":"1975","unstructured":"PANDRIDGE, W, CRC CRITICAL REV TOX: 159 (1975).","journal-title":"CRC CRITICAL REV TOX"},{"key":"e_1_2_1_9_1","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1021\/jm00223a018","volume":"19","year":"1976","unstructured":"SHEK, E, IMPROVED DELIVERY THROUGH BIOLOGICAL-MEMBRANES .2. DISTRIBUTION, EXCRETION, AND METABOLISM OF N-METHYL-1,6-DIHYDROPYRIDINE-2-CARBALDOXIME HYDROCHLORIDE, A PRO-DRUG OF N-METHYLPYRIDINIUM-2-CARBALDOXIME CHLORIDE, JOURNAL OF MEDICINAL CHEMISTRY 19: 108 (1976).","journal-title":"JOURNAL OF MEDICINAL CHEMISTRY"},{"key":"e_1_2_1_10_1","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1021\/jm00223a019","volume":"19","year":"1976","unstructured":"SHEK, E, IMPROVED DELIVERY THROUGH BIOLOGICAL-MEMBRANES .3. DELIVERY OF N-METHYLPYRIDINIUM-2-CARBALDOXIME CHLORIDE THROUGH BLOOD-BRAIN-BARRIER IN ITS DIHYDROPYRIDINE PRO-DRUG FORM, JOURNAL OF MEDICINAL CHEMISTRY 19: 113 (1976).","journal-title":"JOURNAL OF MEDICINAL CHEMISTRY"},{"key":"e_1_2_1_11_1","first-page":"73","volume":"35","year":"1972","unstructured":"SHVAREV, I.F., ANTIBLASTIC PROPERTIES OF BERBERINE AND ITS DERIVATIVES, FARMAKOLOGIYA I TOKSIKOLOGIYA 35: 73 (1972).","journal-title":"FARMAKOLOGIYA I TOKSIKOLOGIYA"}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.7313698","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,15]],"date-time":"2024-01-15T04:39:24Z","timestamp":1705293564000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.7313698"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1981,12,18]]},"references-count":11,"journal-issue":{"issue":"4527","published-print":{"date-parts":[[1981,12,18]]}},"alternative-id":["10.1126\/science.7313698"],"URL":"https:\/\/doi.org\/10.1126\/science.7313698","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[1981,12,18]]}}}