Pharmacology
| Receptor | Quetiapine | Norquetiapine |
|---|---|---|
| D1 | 428 | 99.8 |
| D2 | 626 | 489 |
| 5-HT1A | 1040 | 191 |
| 5-HT2A | 38 | 2.9 |
| α1B | 14.6 | 46.4 |
| α2 | 617 | 1290 |
| H1 | 4.41 | 1.15 |
| M1 | 1086 | 38.3 |
| NET | >10000 | 34.8 |
Quetiapine has the following pharmacological actions:
- D1 (IC50 = 1268nM), D2 (IC50 = 329nM), D3, and D4 receptor antagonist
- 5-HT1A (IC50 = 717nM), 5-HT2A (IC50 = 148nM), 5-HT2C, and 5-HT7 receptor antagonist
- α1-adrenergic (IC50 = 94nM) and α2-adrenergic receptor (IC50 = 271nM) antagonist
- H1 receptor (IC50 = 30nM) antagonist
- mACh receptor (IC50 = >5000nM) antagonist
This means Quetiapine is a dopamine, serotonin, and adrenergic antagonist, and a potent antihistamine with clinically negligible anticholinergic properties. Quetiapine binds strongly to serotonin receptors. Serial PET scans evaluating the D2 receptor occupancy of quetiapine have demonstrated that quetiapine very rapidly disassociates from the D2 receptor. Theoretically, this allows for normal physiological surges of dopamine to elicit normal effects in areas such as the nigrostriatal and tuberoinfundibular pathways, thus minimizing the risk of side-effects such as pseudo-parkinsonism as well as elevations in prolactin. Some of the antagonized receptors (serotonin, norepinephrine) are actually autoreceptors whose blockade tends to increase the release of neurotransmitters.
Norquetiapine is the active metabolite of quetiapine. It has most of the effects of quetiapine with similar potencies, and is also a potent norepinephrine reuptake inhibitor and muscarinic antagonist. Note that the data below is from another source (the official prescribing info for Seroquel), and the measure is different from the above (Ki vs. IC50). There are still order-of-magnitude discrepancies for D1, α1, H1 and M1.
Read more about this topic: Quetiapine