1-(1-Naphthyl) piperazine (1-NP) is a ligand for serotonin (5-hydroxytryptamine, 5-HT) receptors. It acts as an antagonist for 5-HT at 5-HT1 and 5-HT2 in rat cortical membranes with IC50 values of 6 and 1 nM, respectively. 1-NP also blocks contraction in the rat fundus induced by either 5-HT or tryptamine (IC50 = 1 nM for both agonists). 1-NP mimics the 5-HT1 agonist 1-(m-trifluoromethylphenyl)piperazine (TFMPP, ) in decreasing 5-HT receptor turnover and increasing serum corticosterone, suggesting that, in the absence of 5-HT, 1-NP may act as an agonist of the 5-HT1 receptor. However, in squirrel monkeys, 1-NP acts as a non-selective 5-HT receptor antagonist in altering operant behavior. 1-NP also binds to the human 5-HT6 receptor with an affinity comparable to that of 5-HT (Kis = 120 and 100 nM, respectively).
