Related Experiment Video
Updated: Jul 2, 2025

Using Optogenetics to Reverse Neuroplasticity and Inhibit Cocaine Seeking in Rats
Published on: October 5, 2021
The Sobering Sting: Oleoyl Serotonin Is a Novel Stephanoconus Snail Venom-Derived Antagonist of Cannabinoid Receptors
Dongchen An1, Guilherme Salgado Carrazoni2, Ben-Hur Souto das Neves2
1Toxicology and Pharmacology, KU Leuven, Campus Gasthuisberg, ON2, Herestraat 49, Box-922, 3000 Leuven, Belgium.
Abstract:
Cannabinoid receptors (CB1 and CB2) are promising targets for a better understanding of neurological diseases. Nevertheless, only a few ligands of CB have reached clinical application so far. Venoms are considered as interesting sources of novel biologically active compounds. Here, we describe an endocannabinoid-like molecule, oleoyl serotonin (OS), present in the venom of Stephanoconus snails. Using electrophysiological assays, it was shown that OS inhibits CB1 and CB2. Structure-activity relationship studies using a chimeric CB1/2 revealed that the domain encompassing the transmembrane helix V (TMHV)- intracellular loop 3 (ICL3)-TMHVI of the CB2 is critical for the binding and function of OS. We concluded that OS binds to sites of the CB2 that are different from the binding sites of the non-selective CB agonist WIN55,212-2. Behavioral assays in mice showed that OS counteracted learning and memory deficits caused by WIN55,212-2. Furthermore, a selectivity screening of OS showed high selectivity for CB over various ion channels and receptors. Overall, OS may represent a new approach to the prevention and treatment of learning and memory cognition impairment in neurological diseases.
More Related Videos
Related Concept Videos
Ligand-Gated Ion Channel Receptor: Gating Mechanism
Neurochemical Transmission: Sites of Drug Action
Drugs Affecting Neurotransmitter Release or Uptake
Adrenergic Agonists: Indirect-Acting Agents
One mechanism involves depleting stored catecholamines by displacing them from synaptic vesicles. These agents, known as "displacers," are transported into vesicles at the expense of noradrenaline. Examples include amphetamine and tyramine, which lack a catechol moiety, resulting in prolonged action, improved oral...
Role of Neurotransmitters in Memory
Glutamate and Synaptic Plasticity
Glutamate, the brain's main excitatory neurotransmitter, is...
Drugs Affecting Neurotransmitter Synthesis

