| Abstract | The mammalian toxicity of spirolides, a novel group of macrocyclic imines, was first revealed in routine monitoring for diarrhetic shelltïsh poisoning (DSP) toxins from shellfïsh aquaculture sites in Nova Scotia, Canada. Spirolides elicit a novel and highly potent toxic response in mice after intraperitoneal injections. In toxicological studies, the oral and intraperitoneal toxicities of spirolides in mice were determined to be approximately 1 mg kg-’ and 40 μg kg“, respectively. The pharmacological effects of spirolides were also characterized by subjecting mice to various drugs (e.g., atropine, physostigmine, propanolol and epinephrine), followed by a challenge with a spirolide- rich extract of A. ostenfeldii cultures or purified spirolides. Some therapeutants were capable of enhancing survivability, whereas others produced faster death times. After administration of “antidotes” to these therapeutants, and the observationof reversa1 or enhancement of spirolide effects, at least one mode of action was indicated. Spirolides appear to affect the muscarinic acetylcholine receptors in mammalian systems. The potential implications for human health, if any, from consuming spirolide-contaminated shelltïsh have not yet been determined. |
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