Transient receptor potential canonical-6 (TRPC6) channels are non-selective cation channels that can be activated by hyperforin, a constituent of Hypericum perforatum. TRPC6 activation has been linked to a variety of biological functions and pathologies, including focal segmental glomerulosclerosis and the development of various tumor entities. Thus, TRPC6 is an interesting drug target, and a specific pharmacological inhibitor would be very valuable for both basic research and therapy of TRPC6-mediated human pathologies. Here, we assessed the biological activity of various TRP channel inhibitors on hyperforin-stimulated TRPC6 channel signaling. Hyperforin stimulates the activity of the transcription factor AP-1 via TRPC6. Expression experiments involving a TRPC6-specific small hairpin RNA confirmed that hyperforin-induced gene transcription requires TRPC6. Cellular AP-1 activity was measured to assess which compound interrupted the TRPC6-induced intracellular signaling cascade. The results show that the compounds 2-APB, clotrimazole, BCTC, TC-I 2014, SAR 7334, and larixyl acetate blocked TRPC6-mediated activation of AP-1. In contrast, the TRPM8-specific inhibitor RQ-00203078 did not inhibit TRPC6-mediated signaling. 2-APB, clotrimazole, BCTC, and TC-I 2014 are broad-spectrum Ca2+ channel inhibitors, while SAR 7334 and larixyl acetate have been proposed to function as rather TRPC6-specific inhibitors. In this study it is shown that both compounds, in addition to inhibiting TRPC6-induced signaling, completely abolished pregnenolone sulfate-mediated signaling via TRPM3 channels. Thus, SAR 7334 and larixyl acetate are not TRPC6-specific inhibitors.