Pharmacodynamics +<unk>  Site Ki (nM) Action Ref ≥3,676 >10,000 >10,000 5-HT1A 2,063–2,720 Antagonist 5-HT1B 509–660 5-HT1D 540–1,582 5-HT1E 2,010–2,408 5-HT1F 310 5-HT2A 1.32–24.2 Inverse agonist 5-HT2B 11.8–12.0 Inverse agonist 5-HT2C 6.4–29 Inverse agonist 5-HT3 202 Antagonist 5-HT5A 1,212 Full Agonist 5-HT6 6.0–42 Antagonist 5-HT7 105–365 Antagonist α1A 109–115 Antagonist α1B 263 Antagonist α2A 192–470 Antagonist α2B 82–180 Antagonist α2C 29–210 Antagonist β1 >10,000 β2 >10,000 D1 35–118 Antagonist D2 3.00–106 Antagonist D2L 31–38 Antagonist D2S 21–52 Antagonist D3 7.8–91 Antagonist D4 1.6–50 Antagonist D4.2 17–102 Antagonist D4.4 21–60 Antagonist D5 74–90 Antagonist H1 0.65–4.9 Inverse agonist H2 44 Antagonist H3 3,713 Antagonist H4 >10,000 Antagonist M1 2.5–73 Antagonist M2 48–622 Antagonist M3 13–126 Antagonist M4 10–350 Antagonist M5 6.0–82 Antagonist σ1 >5,000 σ2 Opioid >10,000 >10,000 () >10,000 >10,000 >5,000 6,013 Blocker Values are Ki (nM). The smaller the value, the more strongly the drug binds to the site. All data are for human cloned proteins, except H3 (guinea pig), σ1 (guinea pig), opioid (rodent), / (rat), , and .<unk>  has a higher affinity for 5-HT2A serotonin receptors than D2 dopamine receptors, which is a common property of most atypical antipsychotics, aside from the benzamide antipsychotics such as amisulpride along with the nonbenzamides aripiprazole, brexpiprazole, blonanserin, cariprazine, melperone, and perospirone.<unk>  had the highest affinity of any second-generation antipsychotic towards the P-glycoprotein in one in vitro study. P-glycoprotein transports a myriad of drugs across a number of different biological membranes (found in numerous body systems) including the blood-brain barrier (a semipermeable membrane that filters the contents of blood prior to it reaching the brain); P-GP inhibition could mean that less brain exposure to<unk>  results from this interaction with the P-glycoprotein. A relatively large quantity of commonly encountered foods and medications inhibit P-GP, and pharmaceuticals fairly commonly are either substrates of P-GP, or inhibit its action; both substrates and inhibitors of P-GP effectively increase the permeability of the blood-brain barrier to P-GP substrates and subsequently increase the central activity of the substrate, while reducing the local effects on the GI tract. The mediation of<unk>  in the central nervous system by P-GP means that any other substance or drug that interacts with P-GP increases the risk for toxic accumulations of both<unk>  and the other drug.<unk>  is a potent antagonist of the muscarinic M3 receptor, which may underlie its diabetogenic side effects. Additionally, it also exhibits a relatively low affinity for serotonin 5-HT1, GABAA, beta-adrenergic receptors, and benzodiazepine binding sites. The mode of action of<unk> 's antipsychotic activity is unknown. It may involve antagonism of dopamine and serotonin receptors. Antagonism of dopamine receptors is associated with extrapyramidal effects such as tardive dyskinesia (TD), and with therapeutic effects. Antagonism of muscarinic acetylcholine receptors is associated with anticholinergic side effects such as dry mouth and constipation; in addition, it may suppress or reduce the emergence of extrapyramidal effects for the duration of treatment, but it offers no protection against the development of TD. In common with other second-generation (atypical) antipsychotics,<unk>  poses a relatively low risk of extrapyramidal side effects including TD, due to its higher affinity for the 5HT2A receptor over the D2 receptor. Antagonizing H1 histamine receptors causes sedation and may cause weight gain, although antagonistic actions at serotonin 5-HT2C and dopamine D2 receptors have also been associated with weight gain and appetite stimulation. Pharmacokinetics Metabolism<unk>  is metabolized by the cytochrome P450 (CYP) system; principally by isozyme 1A2 (CYP1A2) and to a lesser extent by CYP2D6. By these mechanisms, more than 40% of the oral dose, on average, is removed by the hepatic first-pass effect. Clearance of<unk>  appears to vary by sex; women have roughly 25% lower clearance than men. Clearance of<unk>  also varies by race; in self-identified African Americans or Blacks,<unk> 's clearance was 26% higher. A difference in the clearance is not apparent between individuals identifying as Caucasian, Chinese, or Japanese. Routine, pharmacokinetic monitoring of<unk>  plasma levels is generally unwarranted, though unusual circumstances (e.g. the presence of drug-drug interactions) or a desire to determine if patients are taking their medicine may prompt its use. Chemistry<unk>  is unusual in having four well-characterised crystalline polymorphs and many hydrated forms.
Olanzapine
Aripiprazole
Risperidone
Ziprasidone
Clozapine
Sertraline
Electroconvulsive therapy
Lorpiprazole