{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T12:54:17Z","timestamp":1791118457805,"version":"4.1.0"},"reference-count":42,"publisher":"American Chemical Society (ACS)","issue":"5","license":[{"start":{"date-parts":[[2017,12,29]],"date-time":"2017-12-29T00:00:00Z","timestamp":1514505600000},"content-version":"vor","delay-in-days":4705,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Symptoms consistent with inhalation toxicity have long been associated with Florida red tides, and various causal agents have been proposed. Research since 1981 has centered on a group of naturally occurring trans-fused cyclic polyether compounds called brevetoxins that are produced by a marine dinoflagellate known as Karenia brevis. Numerous individual brevetoxins have been identified from cultures as well as from natural bloom events. A spectrum of brevetoxin derivatives produced by chemical modification of the natural toxins has been prepared to examine the effects of functional group modification on physiologic activity. Certain structural features of natural and synthetic derivatives of brevetoxin appear to ascribe specific physiologic consequences to each toxin. Differential physiologic effects have been documented with many of the natural toxins and derivatives, reinforcing the hypothesis that metabolism or modification of toxin structures modulates both the specific toxicity (lethality on a per milligram basis) and potentially the molecular mechanism(s) of action. A series of naturally occurring fused-ring polyether compounds with fewer rings than brevetoxin, known as brevenals, exhibit antagonistic properties and counteract the effects of the brevetoxins in neuronal and pulmonary model systems. Taken together, the inhalation toxicity of Florida red tides would appear to depend on the amount of each toxin present, as well as on the spectrum of molecular activities elicited by each toxin. Toxicity in a bloom is diminished by the amount brevenal present.<\/jats:p>","DOI":"10.1289\/ehp.7499","type":"journal-article","created":{"date-parts":[[2005,2,10]],"date-time":"2005-02-10T14:10:50Z","timestamp":1108044650000},"page":"621-625","source":"Crossref","is-referenced-by-count":204,"title":["Natural and Derivative Brevetoxins: Historical Background, Multiplicity, and Effects"],"prefix":"10.1021","volume":"113","author":[{"given":"Daniel G.","family":"Baden","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea J.","family":"Bourdelais","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"Jacocks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Michelliza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerome","family":"Naar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2005,2,10]]},"reference":[{"key":"2026080607023202600_micit1","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1289\/ehp.7498","article-title":"Effects of inhaled brevetoxins in allergic airways: toxin\u2013allergen interactions and pharmacologic intervention","volume":"113","author":"Abraham","year":"2005","journal-title":"Environ Health Perspect"},{"key":"2026080607023202600_micit2","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1289\/ehp.7502","article-title":"Occupational exposure to aerosolized brevetoxins during Florida red tide events: effects on a healthy worker population","volume":"113","author":"Backer","year":"2005","journal-title":"Environ Health Perspect"},{"key":"2026080607023202600_micit3","author":"Baden"},{"key":"2026080607023202600_micit4","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0074-7696(08)60824-4","article-title":"Marine food-borne dinoflagellate toxins","volume":"82","author":"Baden","year":"1983","journal-title":"Int Rev Cytol"},{"key":"2026080607023202600_micit5","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1096\/fasebj.3.7.2565840","article-title":"Biochemistry of the brevetoxins: potent activators of voltage-sensitive sodium channels","volume":"3","author":"Baden","year":"1989","journal-title":"FASEB J"},{"key":"2026080607023202600_micit6","author":"Baden"},{"key":"2026080607023202600_micit7","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/0041-0101(82)90009-5","article-title":"Toxicity of two toxins isolated from Ptychodiscus brevis","volume":"20","author":"Baden","year":"1981","journal-title":"Toxicon"},{"key":"2026080607023202600_micit8","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/0041-0101(84)90161-2","article-title":"Specific antibodies directed against toxins of Ptychodiscus brevis","volume":"22","author":"Baden","year":"1984","journal-title":"Toxicon"},{"key":"2026080607023202600_micit9","author":"Baden"},{"key":"2026080607023202600_micit10","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1016\/0041-0101(88)90261-9","article-title":"Variations in major toxin composition for six clones of Ptychodiscus brevis","volume":"26","author":"Baden","year":"1988","journal-title":"Toxicon"},{"key":"2026080607023202600_micit11","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1289\/ehp.7497","article-title":"Inhalation toxicity of brevetoxin 3 in rats exposed for twenty-two days","volume":"113","author":"Benson","year":"2005","journal-title":"Environ Health Perspect"},{"issue":"1-S","key":"2026080607023202600_micit12","first-page":"807","article-title":"Toxic brevetoxin complexes are in aqueous solutions [Abstract]","volume":"78","author":"Bourdelais","year":"2004","journal-title":"Toxicologist"},{"key":"2026080607023202600_micit13","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1023\/B:CEMN.0000023629.81595.09","article-title":"Brevenal is a natural inhibitor of brevetoxin action in sodium channel receptor binding assays","volume":"24","author":"Bourdelais","year":"2004","journal-title":"Cell Mol Neurobiol"},{"key":"2026080607023202600_micit14","author":"Bourdelais"},{"key":"2026080607023202600_micit15","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1021\/np049797o","article-title":"A new polyether ladder compound produced by the dinoflagellate Karenia brevis","volume":"68","author":"Bourdelais","year":"2005","journal-title":"J Nat Prod"},{"key":"2026080607023202600_micit16","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/S0026-895X(25)13490-1","article-title":"Toxin T46 from Gymnodinium breve (formerly Ptychodiscus brevis) enhances activation of voltage-sensitive sodium channels by veratridine","volume":"19","author":"Catterall","year":"1981","journal-title":"Mol Pharmacol"},{"key":"2026080607023202600_micit17","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1289\/ehp.7496","article-title":"Characterization of marine aerosol for assessment of human exposure to brevetoxins","volume":"113","author":"Cheng","year":"2005","journal-title":"Environ Health Perspect"},{"key":"2026080607023202600_micit18","doi-asserted-by":"crossref","first-page":"2865","DOI":"10.1016\/S0040-4039(00)98857-9","article-title":"Isolation and structure of two new polycyclic ethers from Gymnodinium breve Davis (= Ptychodiscus brevis)","volume":"26","author":"Chou","year":"1985","journal-title":"Tetrahedron Lett"},{"key":"2026080607023202600_micit19","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1289\/ehp.7500","article-title":"Initial evaluation of the effects of aerosolized Florida red tide toxins (brevetoxins) in persons with asthma","volume":"113","author":"Fleming","year":"2005","journal-title":"Environ Health Perspect"},{"key":"2026080607023202600_micit20","first-page":"1","article-title":"Red tide. Spec","volume":"46","author":"Galtsoff","year":"1948","journal-title":"Sci Rep US Fish Wildl Serv"},{"key":"2026080607023202600_micit21","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/1074-5521(95)90187-6","article-title":"The relationship of brevetoxins \u201clength\u201d and A-ring functionality to binding and activity in neuronal sodium channels","volume":"2","author":"Gawley","year":"1995","journal-title":"Chem Biol"},{"key":"2026080607023202600_micit22","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1016\/0041-0101(92)90014-V","article-title":"Binding of brevetoxins and ciguatoxin to the voltage-sensitive sodium channel and conformational analysis of brevetoxin B","volume":"30","author":"Gawley","year":"1992","journal-title":"Toxicon"},{"key":"2026080607023202600_micit23","first-page":"1","article-title":"Irritant gas associated with red tide","volume":"9","author":"Ingle","year":"1954","journal-title":"Mar Lab Univ Miami Spec Serv Bull"},{"key":"2026080607023202600_micit24","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/S0022-3565(24)37263-5","article-title":"Brevetoxin-3 (PbTx-3) and its derivatives modulate single tetrodotoxin-sensitive sodium channels in rat sensory neurons","volume":"284","author":"Jeglitsch","year":"1998","journal-title":"J Pharmacol Exp Ther"},{"key":"2026080607023202600_micit25","doi-asserted-by":"crossref","first-page":"6773","DOI":"10.1021\/ja00412a053","article-title":"Isolation and structure of brevetoxin B from \u201cred tide\u201d dionoflagellate Gymnodinium breve (Ptychodiscus brevis)","volume":"103","author":"Lin","year":"1981","journal-title":"J Am Chem Soc"},{"key":"2026080607023202600_micit26","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/221059a0","article-title":"Isolation and characterization of a toxin from the Florida red tide organism","volume":"221","author":"Martin","year":"1969","journal-title":"Nature"},{"key":"2026080607023202600_micit27","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/0041-0101(65)90005-X","article-title":"The occurrence of a ciguatera-like poisons in oysters, clams, and Gymnodinium breve cultures","volume":"3","author":"McFarren","year":"1965","journal-title":"Toxicon"},{"key":"2026080607023202600_micit28","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1021\/ja00108a052","article-title":"Total synthesis of brevetoxin B. 2. Completion","volume":"117","author":"Nicoloau","year":"1995","journal-title":"J Am Chem Soc"},{"key":"2026080607023202600_micit29","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1038\/32623","article-title":"Total synthesis of brevetoxin A","volume":"392","author":"Nicoloau","year":"1998","journal-title":"Nature"},{"key":"2026080607023202600_micit30","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/S0026-895X(25)10324-6","article-title":"Brevetoxins, unique activators of voltage sensitive sodium channels, bind to specific sites in rat brain synaptosomes","volume":"30","author":"Poli","year":"1986","journal-title":"Mol Pharmacol"},{"key":"2026080607023202600_micit31","first-page":"909","article-title":"Brevetoxin modulates neuronal sodium channels in two cell lines derived from rat brain","volume":"20","author":"Purkerson","year":"1999","journal-title":"Neurotoxicology"},{"key":"2026080607023202600_micit32","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/S1074-5521(00)00119-8","article-title":"Brevetoxin derivatives that inhibit toxin activity","volume":"7","author":"Purkerson-Parker","year":"2000","journal-title":"Chem Biol"},{"key":"2026080607023202600_micit33","doi-asserted-by":"crossref","first-page":"2101","DOI":"10.1021\/jo00087a027","article-title":"Conformational analysis of the sodium channel modulator brevetoxin a, comparison with brevetoxin B conformations, and an hypothesis about the common pharmacophore of the \u201csite 5\u201d toxins","volume":"59","author":"Rein","year":"1994","journal-title":"J Org Chem"},{"key":"2026080607023202600_micit34","doi-asserted-by":"crossref","first-page":"2107","DOI":"10.1021\/jo00087a028","article-title":"Brevetoxin B: chemical modifications, synaptosome binding, toxicity, and an unexpected conformational effect","volume":"59","author":"Rein","year":"1994","journal-title":"J Org Chem"},{"key":"2026080607023202600_micit35","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1021\/ja00263a031","article-title":"Structure of brevetoxin A (gb-1), the most potent toxin in the Florida red tide organism (Gymnodinium breve)","volume":"108","author":"Shimizu","year":"1986","journal-title":"J Am Chem Soc"},{"key":"2026080607023202600_micit36","author":"Shimizu"},{"key":"2026080607023202600_micit37","author":"Steidinger"},{"key":"2026080607023202600_micit38","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/BF00123378","article-title":"An approach to computer aided inhibitor design: application to cathepsin l","volume":"6","author":"Sudaranam","year":"1992","journal-title":"J Comput Aided Mol Des"},{"key":"2026080607023202600_micit39","first-page":"112","article-title":"Evolutions: the voltage-gated sodium channel","volume":"6","author":"Taylor","year":"1994","journal-title":"J NIH Res"},{"key":"2026080607023202600_micit40","doi-asserted-by":"crossref","first-page":"19904","DOI":"10.1016\/S0021-9258(17)32105-1","article-title":"Identification of the peptide components of the brevetoxin receptor site of rat brain sodium channels","volume":"269","author":"Trainer","year":"1994","journal-title":"J Biol Chem"},{"key":"2026080607023202600_micit41","first-page":"56","article-title":"Note concerning human respiratory irritation associated with high concentrations of plankton and mass mortalities of marine organisms","volume":"7","author":"Woodcock","year":"1948","journal-title":"J Mar Res"},{"key":"2026080607023202600_micit42","first-page":"55","article-title":"Microorganisms in marine air","volume":"17","author":"Zobell","year":"1942","journal-title":"Aerobiology (AAAS)"}],"container-title":["Environmental Health Perspectives"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/evhpaz\/article-pdf\/113\/5\/621\/66435185\/ehp.7499.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/evhpaz\/article-pdf\/113\/5\/621\/66435185\/ehp.7499.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T13:46:45Z","timestamp":1786628805000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/evhpaz\/article-lookup\/doi\/10.1289\/ehp.7499"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,2,10]]},"references-count":42,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2005,2,10]]},"published-print":{"date-parts":[[2005,5,1]]}},"URL":"https:\/\/doi.org\/10.1289\/ehp.7499","relation":{},"ISSN":["0091-6765","1552-9924"],"issn-type":[{"value":"0091-6765","type":"print"},{"value":"1552-9924","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,2,10]]}}}