Table 1.
(A) Inhibitory effect (IC50 values) of fenamates on transient receptor potential (TRP) channels
| TRPC6 | TRPM2 | TRPM3 | TRPV4 | |
|---|---|---|---|---|
| DCDPC | 16.4 ± 3.1 µM | 31.1 ± 3.4 µM | 7.5 ± 4.7 µM | 8.6 ± 1.8 µM |
| Flufenamic acid | 17.1 ± 7.2 µM | 155.1 ± 50.6 µM | 33.1 ± 8.3 µM | 40.7 ± 10.3 µM |
| Niflumic acid | 40.2 ± 20.1 µM | >300 µM | 123.5 ± 24.3 µM | 84.4 ± 11.9 µM |
| Mefenamic acid | >300 µM | >300 µM | 6.6 ± 1.8 µM | >300 µM |
| Meclofenamic acid | 37.5 ± 14.4 µM | 75.8 ± 33.6 µM | 13.3 ± 3.5 µM | 40.7 ± 10.2 µM |
| S645648 | >300 µM | >300 µM | >300 µM | >300 µM |
| Tolfenamic acid | 12.3 ± 4.8 µM | 96.1 ± 10.8 µM | 11.1 ± 2.7 µM | 23.9 ± 7.1 µM |
| (B) Rank order of fenamates according to their potencies in blocking transient receptor potential (TRP) channels | ||||
|---|---|---|---|---|
| TRPC6 | TOL ∼ DCDPC ∼ FLU > MEC ∼ NIF > S645648, MEF | |||
| TRPM2 | DCDPC > MEC > TOL > FLU > NIF, S645648, MEF | |||
| TRPM3 | MEF > DCDPC > TOL ∼ MEC > FLU > NIF > S645648 | |||
| TRPV4 | DCDPC > TOL > FLU, MEC > NIF > S645648, MEF | |||
| (C) Rank order of transient receptor potential (TRP) channels most potently blocked by each fenamate | ||||
|---|---|---|---|---|
| DCDPC | TRPM3 ∼ TRPV4 > TRPC6 > TRPM2 | |||
| Flufenamic acid | TRPC6 > TRPM3 > TRPV4 > TRPM2 | |||
| Niflumic acid | TRPC6 > TRPV4 > TRPM3 > TRPM2 | |||
| Mefenamic acid | TRPM3 >> TRPV4, TRPC6, TRPM2 | |||
| Meclofenamic acid | TRPM3 > TRPC6 ∼ TRPV4 > TRPM2 | |||
| Tolfenamic acid | TRPM3 ∼ TRPC6 > TRPV4 > TRPM2 | |||
In (A) changes in [Ca2+]i were measured using FLIPRTetra as described in Methods (n = 4–6).
Bold type in (B) highlights the selectivity of mefenamic acid in blocking TRPM3.