Methylaplysinopsin: a natural product of marine origin with effects on serotonergic neurotransmission.
1. Methylaplysinopsin is an indolyl-methylene derivative of creatinin which was isolated from a sponge collected on the Great Barrier Reef. 2. It is a potent inhibitor of tetrabenazine-induced responses in rats and mice and appears to act through several mechanisms, each of which enhances central serotonergic function. 3. As a reversible inhibitor of type A monoamine oxidase (MAO) methylaplysinopsin is relatively short-acting and has a Ki of 0.2 mumol/l when serotonin is the substrate used. 4. Methylaplysinopsin (10(-4) mol/l) also releases [3H]-serotonin from prelabelled synaptosomes, but has little effect on release of [3H]-noradrenaline ([3H]-NA) from a similar preparation. 5. In blocking uptake of [3H]-serotonin into cerebral cortical synaptosomes, methylaplysinopsin has a potency similar to that of imipramine (Ki = 2 X 10(-7) mol/l cf. 5 X 10(-7) mol/l), but it is considerably less potent in blocking [3H]-NA uptake. 6. Methylaplysinopsin is a weak displacer of [3H]-serotonin specific binding (IC50 = 160 mumol/l for hippocampal membrane preparations and 66 mumol/l for crude homogenates of rat brain). 7. Thus, methylaplysinopsin has effects on various aspects of serotonergic function. Whilst some of these effects are weak, they appear relatively selective for this neurochemical system.
D000818:Animals; D000928:Antidepressive Agents / Q000378:metabolism / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D007700:Kinetics; D008297:Male; D051379:Mice; D008996:Monoamine Oxidase Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects; D013747:Tetrabenazine / Q000037:antagonists & inhibitors; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
D000928:Antidepressive Agents; D008996:Monoamine Oxidase Inhibitors; D011985:Receptors, Serotonin; D012701:Serotonin; C028093:methylaplysinopsin; D014364:Tryptophan; D013747:Tetrabenazine