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.