L-Tetrahydropalmatine (L-THP) vs Tropisetron

Cognitive

Cognitive

Research Only

Research Only

L-THP acts as a mixed dopamine receptor antagonist, binding D1 (Ki ~124 nM), D2 (Ki ~388 nM), and D3 receptors (Ki ~1420 nM), with additional affinity for serotonin 5-HT1A receptors (Ki ~340 nM) and alpha-1 adrenergic receptors; it also facilitates GABA-A receptor binding. In vivo microdialysis in rats indicates predominantly postsynaptic (not presynaptic) dopamine receptor antagonism underlies its effects on drug reward. L-THP modestly elevates extracellular nucleus accumbens dopamine alone but dose-dependently potentiates cocaine-induced dopamine elevation while reducing cocaine’s rewarding effects, consistent with postsynaptic antagonism.

Tropisetron acts as a selective competitive antagonist at 5-HT3 serotonin receptors, the basis of its approved antiemetic use. It also functions as a partial agonist at α7 nicotinic acetylcholine receptors, demonstrated in Xenopus oocytes expressing human α7/α4β2/α3β4 nAChR and rat 5-HT3A receptors, with the tropane moiety identified as the minimal α7 pharmacophore. A separate study reported that low-nanomolar tropisetron (10–30 nM) sensitizes α7 and α7β2 currents to submaximal acetylcholine rather than acting as a conventional orthosteric agonist at those concentrations.