Pharmacology of systemically administered domoic acid in mice. 1991

R A Tasker, and B J Connell, and S M Strain
Department of Anatomy and Physiology, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, P.E.I., Canada.

Domoic acid, a structural analogue of kainic acid, has been identified as the toxin that poisoned people who consumed contaminated blue mussels harvested from eastern Prince Edward Island in December of 1987. To investigate the pharmacology of domoic acid in vivo we injected groups of mice with serial dilutions of extracts of contaminated mussels and verified domoic acid concentrations using high performance liquid chromatography. Mice progressed through a series of behavioural changes that were both reproducible and dose-dependent. These behaviours formed the basis of a rating scale that was used to reliably quantitate domoic acid concentrations as low as 20 micrograms/mL. This scale was then used to compare the relative toxicity of domoic acid contained in four formulations: namely, (1) extracts of contaminated mussels, (2) pure domoic acid, (3) extracts of noncontaminated mussels that were "spiked" with pure domoate, and (4) extracts of the algal source of domoic acid. Interpolation of the resulting dose-response curves produced median toxic dose (TD50) values of 2.9, 3.9, 4.9, and 4.2 mg/kg for the four formulations, respectively. Statistical analysis of these data revealed that curves for all formulations of domoic acid were parallel, but that extracts of contaminated mussels were significantly more potent than any of the other formulations at low and intermediate doses of domoic acid. We further compared domoic acid toxicity with that produced by kainic acid. Dose-response curves for both compounds were statistically parallel and both toxins were equally efficacious. The TD50 values were 3.9 and 31.9 mg/kg for pure domoic acid and kainic acid, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

UI MeSH Term Description Entries
D007608 Kainic Acid (2S-(2 alpha,3 beta,4 beta))-2-Carboxy-4-(1-methylethenyl)-3-pyrrolidineacetic acid. Ascaricide obtained from the red alga Digenea simplex. It is a potent excitatory amino acid agonist at some types of excitatory amino acid receptors and has been used to discriminate among receptor types. Like many excitatory amino acid agonists it can cause neurotoxicity and has been used experimentally for that purpose. Digenic Acid,Kainate,Acid, Digenic,Acid, Kainic
D009467 Neuromuscular Depolarizing Agents Drugs that interrupt transmission at the skeletal neuromuscular junction by causing sustained depolarization of the motor end plate. These agents are primarily used as adjuvants in surgical anesthesia to cause skeletal muscle relaxation. Depolarizing Muscle Relaxants,Muscle Relaxants, Depolarizing,Depolarizing Blockers,Agents, Neuromuscular Depolarizing,Blockers, Depolarizing,Depolarizing Agents, Neuromuscular,Relaxants, Depolarizing Muscle
D002851 Chromatography, High Pressure Liquid Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed. Chromatography, High Performance Liquid,Chromatography, High Speed Liquid,Chromatography, Liquid, High Pressure,HPLC,High Performance Liquid Chromatography,High-Performance Liquid Chromatography,UPLC,Ultra Performance Liquid Chromatography,Chromatography, High-Performance Liquid,High-Performance Liquid Chromatographies,Liquid Chromatography, High-Performance
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005260 Female Females
D005506 Food Contamination The presence in food of harmful, unpalatable, or otherwise objectionable foreign substances, e.g. chemicals, microorganisms or diluents, before, during, or after processing or storage. Food Adulteration,Adulteration, Food,Adulterations, Food,Contamination, Food,Contaminations, Food,Food Adulterations,Food Contaminations
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001522 Behavior, Animal The observable response an animal makes to any situation. Autotomy Animal,Animal Behavior,Animal Behaviors
D049872 Bivalvia A class in the phylum MOLLUSCA comprised of mussels; clams; OYSTERS; COCKLES; and SCALLOPS. They are characterized by a bilaterally symmetrical hinged shell and a muscular foot used for burrowing and anchoring. Mussels,Bivalves,Clams,Bivalve,Bivalvias,Clam,Mussel
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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