Methylaplysinopsin and other marine natural products affecting neurotransmission

Methylaplysinopsin is a novel marine natural product that, after oral administration, prevented the effects of tetrabenazine in mice and rats. Methylaplysinopsin was a short-acting inhibitor of monoamine oxidase activity with greatest potency when serotonin was the substrate studied. The brain concentration of serotonin in the mouse was increased by methylaplysinopsin over the same time course as monoamine oxidase inhibition ex vivo. Methylaplysinopsin was also a weak inhibitor of the neuronal uptake of [3H]serotonin and a potentiator of the K+-induced release of [3H]serotonin from prelabeled synaptosomes. The predicted potentiation of serotonergic neurotransmission was supported by initial neurophysiological studies in an identified serotonergic pathway in the central nervous system of Aplysia. Two other studies on the pharmacology of marine natural products are reviewed. The majority of polyhalogenated monoterpenes isolated from red algae had central nervous system depressant properties. The exception is plocamadiene A, which caused, in mice, a reversible spastic paresis lasting up to 72 hours after oral administration. The severe muscle spasm was antagonized by diazepam. The final study discussed is the effect of a variety of marine natural products on the synthesis, neuronal uptake, and metabolism of GABA. Their selectivity is discussed with regard to the effects on metabolic respiration, and the correlation of neurochemical and neurophysiological effects on these marine substances.