Table 1.
Inhibition of [3H]MK-801 and [3H]ifenprodil binding to rat cortical membranes by pentamidine analogs with heteroatom variations in the bridge
 | |||||||
|---|---|---|---|---|---|---|---|
| X | YRY | RP | [3H]MK-801 | [3H]ifenprodil | |||
| IC50 ± SD (n) (µM) | Ratio | IC50 ± SD (n) | |||||
| No spm | 30 µM spm | No spm | |||||
| Arcaine | — | — | — | 4.60 ± 1.71 (4) | 196 (2) | 33.6 (2) | 24.4 (2) |
| N12N | — | — | — | 7.05 ± 2.38 (11) | 245 ± 30 (5) | 32.9 ± 6.3 (5) | 960 (2) |
| N4T8N | — | — | — | 0.52 ± 0.32 (46) | 6.10 ± 1.43 (24) | 15.1 ± 7.1 (24) | 49.3 (2) |
| 1 | O | CH2 | — | 2.68 ± 0.65 (9) | 24.9 ± 5.7 (7) | 9.1 ± 2.5 (7) | 32.5 (2) |
| 2 | O | O | — | 3.41 ± 0.52 (4) | 148 ± 22 (3) | 40.6 ± 4.2 (3) | 63.8 (2) |
| 3 | O | O | OMe | 10.6 ± 3.9 (4) | 343 ± 27 (3) | 33.1 ± 11.7 (3) | 43.7 (2) |
| 4 | O | S | — | 2.20 ± 0.32 (3) | 29.1 (2) | 12.3 (2) | 19.2 (2) |
| 5 | S | O | — | 1.22 ± 0.23 (3) | 23.8 ± 2.7 (3) | 20.2 ± 6.1 (3) | n.d. |
| 6 | O | O | — | 317 ± 20 (3) | 785 (2) | 2.59 (2) | n.d. |
| 7 | NH | CH2 | — | 3.10 ± 0.11 (3) | 42.3 ± 1.9 (3) | 13.7 ± 0.6 (3) | 20.6 ± 5.4 (3) |
| 8 | NMe | CH2 | — | 0.56 ± 0.08 (4) | 5.62 ± 2.88 (4) | 9.2 ± 3.5 (4) | 16.6 (2) |
| 9 | NH | CH2 | OMe | 2.88 (2) | 20.7 (2) | 7.2 (2) | 4.54 ± 1.43 (3) |
| 10 | NH | O | — | 0.85 ± 0.23 (7) | 38.5 ± 10.4 (6) | 50.6 ± 19.7 (6) | 11.4 ± 3.7 (3) |
| 11 | NMe | O | — | 0.76 ± 0.15 (4) | 12.5 ± 1.8 (3) | 15.2 ± 2.2 (3) | 21.9 ± 5.2 (3) |
| 12 | O | NH+Me | — | 21.2 ± 5.1 (3) | 143 (2) | 7.65 (2) | n.d. |
| 13 | O | N-Bs | — | 0.23 ± 0.06 (4) | 2.13 ± 0.17 (3) | 10.4 ± 1.56 (3) | 1.47 ± 0.55 (3) |
| 14 | O | NTs | — | 0.24 ± 0.08 (5) | 1.32 ± 0.23 (4) | 6.28 ± 1.18 (4) | 0.41 ± 0.13 (3) |
| 15 | O | NTs | OMe | 3.77 ± 1.37 (4) | 28.7 ± 4.4 (3) | 8.11 ± 2.91 (3) | 0.84 ± 0.48 (4) |
Number of experiments (n) in parentheses; if n = 2, no SD is indicated (see Supporting information for single values); spm, spermine; n.d., not determined. The column ‘ratio’ lists the mean ratios IC50 (30 µM spm)/IC50 (no spm). N12N, diaminododecane; N4T8N, 5-(4-aminobutyl)-2-thiopheneoctanamine;41 Bs, benzenesulfonyl.