Vapreotide is an antagonist of the neurokinin-1 (NK1) receptor (IC50: 330 nM).

NK1R:330 nM

In a concentration-dependent manner, Vapreotide attenuates the effect of SP on calcium release . The concentration required for Vapreotide to completely inhibit the effect of SP is about 100 times higher than that required for the NK1R antagonist aprepitant. The effect of Vapreotide on cell proliferation is mediated primarily by SSTR2. In order to further establish the NK1R antagonist effect of Vapreotide, U373MG cells are pretreated with SSTR2 selective antagonist CYN followed by incubation with Vapreotide and SP stimulation. The results show that pretreatment with CYN does not reverse the inhibitory effect of Vapreotide on SP-stimulated IL-8 mRNA expression. As compared to control MDM, limited HIV gag mRNA expression may indicate that Vapreotide can reduce HIV-1 replication in MDM. In addition, SP treatment (10 μM) reversed the inhibitory effect of pentoprofen on HIV-1 replication in MDM. This observation indicates that the inhibitory effect of Vapreotide on HIV-1 replication is most likely due to its interaction with NK1R.