Table 2.
Inhibition of the MSR by 5-HT1B agonists
| Receptor Activation | Inhibition of the MSR | Comparison with 5-HT1D Affinity |
|||||
|---|---|---|---|---|---|---|---|
| Agonist | Antagonist present | Receptors that can be activated | Efficacy, %change | pEC50 (−log EC50) | EC50, nM | pKi at 5-HT1D (−log Ki) | Relative potency (pKi − pEC50) |
| Zolmitriptan | None | 5-HT1B,1D,1F | −63.54 ± 20.35* | 8.36 ± 0.31 | 4.40 | 9.20 | −0.86 |
| Zolmitriptan | SB224289 | 5-HT1D,1F | −72.60 ± 31.07* | 8.45 ± 0.25 | 3.53 | 9.20 | −0.75 |
| Methylergonovine | None | 5-HT1B,1D,1E,1F, 5-HT2,7 | −79.24 ± 38.39* | 8.42 ± 0.17 | 3.80 | 9.20 | −0.78 |
| 5-HT | None | All 5-HTRs | −28.88 ± 11.12* | 7.62 ± 0.38 | 23.99 | 8.60 | −0.98 |
| Methysergide | None | 5-HT1D,1F, 5-HT2,5,6,7 | −93.8 ± 2.90* | 7.00 ± 0.30 | 100.00 | 8.11 | −1.11 |
| LSD | None | 5-HT1A,1B,1D,1E, 5-HT2,5,6,7 | −55.11 ± 28.95* | 6.59 ± 0.15 | 252.27 | 7.90 | −1.31 |
| α-Methyl-5-HT | None | 5-HT1B,1D,1E,1F, 5-HT2,4 | −58.75 ± 20.92* | 6.12 ± 0.17 | 765.72 | 6.82 | −0.70 |
| α-Methyl-5-HT | SB206553 | 5-HT1B,1D,1E,1F, 5-HT4 | −62.21 ± 27.20* | 6.10 ± 0.25 | 793.46 | 6.82 | −0.72 |
| 2-Methyl-5-HT | Granisetron | 5-HT1D, 5-HT2B,6 | −53.87 ± 26.89* | 5.28 ± 0.40 | 5263.23 | 6.40 | −1.12 |
| Zolmitriptan | SB216664 | 5-HT1F | −43.72 ± 27.41*† | 6.77. ± 0.51*† | 169.82 | ||
| α-Methyl-5-HT | GR127935 | 5-HT1E,1F, 5-HT2,4 | −3.99 ± 25.67*† | ND | ND | ||
| LY344864 | None | 5-HT1F | 1.55 ± 7.82 | ND | ND | ||
| DOI | None | 5-HT2A,2B,2C | 1.04 ± 3.89 | ND | ND | ||
| MK-212 | None | 5-HT2C,3 | −2.85 ± 34.10 | ND | ND | ||
| LP44 | None | 5-HT1A, 5-HT7 | 0.51 ± 12.64 | ND | ND | ||
| 8-OH-DPAT | None | 5-HT1A, 5-HT5,7 | −8.08 ± 32.42 | ND | ND | ||
| EMD386088 | GR127935 | 5-HT6 | −2.01 ± 12.32 | ND | ND | ||
Agonists with varying selectivity for the different 5-HT receptors were applied to chronic spinal rats, sometimes after prior application of 5-HT receptor antagonists to effectively make the agonist action more selective (pretreatment). The receptors that can be activated by this agonist/antagonist combination are indicated in (Ki < 400 nM; see details in Table 1). The antagonists used in combination with some drugs were SB216641 (5-HT1D/1B receptor antagonist; 3 µM), SB224289 (5-HT1B; 3 µM), GR127935 (5-HT1D/1B; 3 µM), SB206553 (5-HT2; 3 µM), and granisetron (5-HT3; 3 µM). The efficacy of these agonists in inhibiting the MSR is indicated, normalized by the predrug reflex amplitudes [100 × (postdrug − predrug)/predrug]. The potency and EC50 of these drugs at inhibiting the monosynaptic stretch reflex (MSR) are also indicated. ND, no change in efficacy with drug, and so no EC50 or potency could be detected. The relative potency is computed from the affinity and potency, as indicated.
P < 0.05, significant change in reflex with drug (efficacy); n > 8 per condition.
P < 0.05, significant decrease in potency of 5-HT after application of antagonist; n > 8 per condition.