Potencies of various histamine derivatives at NMDAR-mediated responses
For agonists, data are EC50 (micromolar) values, relative potency, and intrinsic activity (in parentheses, respectively). For antagonists/inverse agonists, data are IC50 (micromolar) values. The EC50 values on [3H]noradrenaline release were obtained from the concentration-response curves shown in Figs. 3 and 4. The relative potencies were determined by comparison with that of histamine (=100). The intrinsic activities were determined by comparison with the maximal effect of histamine.
| Potentiation of [3H]Noradrenaline Release | Potentiation of NMDA Currents | Property at Brain Histaminergic Receptors | |
|---|---|---|---|
| Agonist | |||
| Histamine | 99 ± 17 (100) (1) | 1.7 −10a,b,c (100) (1) | Agonist |
| Histidine | No effect at 100 | No effect at 100c | Not active |
| 4-Methylimidazole | 93 ± 10 (106) (1) | Not tested | Not active |
| pros-Methylhistamine | No effect at 100 | No effect at 10c | Not active |
| tele-Methylhistamine | 97 ± 22 (102) (1) | 7.2 ± 1.5 (122) (1) | Not active |
| Nα-Methylhistamine | No effect at 100 | No effect at 10c | Agonist |
| Nα,Nα-Dimethylhistamine | No effect at 100 | Not tested | Agonist |
| (R)-α-Methylhistamine | 41 ± 24 (241) (0.3) | EC50 ≈ 10c (100) | H3-Agonist |
| Burimamide | 6 ± 2 (1650) (0.4) | Not tested | H2/H3-Antagonist |
| 2-Pyridylethylamine | 5 ± 0.5 (1980) (1) | Not tested | H1-Agonist |
| Antagonist/inverse agonist | |||
| Impromidine | 15 ± 3 | ≈10b | H2-Agonist/H3-antagonist |
| Imetit | Inhibitory effect at 100 | Inhibitory effect at 10c | H3-Agonist |
| Thioperamide | No effect at 2 | No effect at 10b | H3-Antagonist |