Pharmacodynamics +<unk>  Site Ki (nM) IA (%) Action 5-HT1A 2.6 Partial agonist 5-HT2A 18.8 Antagonist 5-HT2B 0.58 Antagonist 5-HT2C 134 Inverse agonist 5-HT7 111 Antagonist α1A 155 Antagonist D2L 0.49 ~40% Partial agonist D2S 0.69 ~40% Partial agonist D3 0.085 ~60% Partial agonist H1 23.2 Antagonist >1,000 Antagonist The smaller the Ki value, the more strongly the drug binds to the site. IA=intrinsic activity. Unlike many antipsychotics that are D2 and 5-HT2A receptor antagonists,<unk>  is a D2 and D3 partial agonist. It also has a higher affinity for D3 receptors. The D2 and D3 receptors are important targets for the treatment of schizophrenia, because the overstimulation of dopamine receptors has been implicated as a possible cause of schizophrenia.<unk>  acts to inhibit overstimulated dopamine receptors (acting as an antagonist) and stimulate the same receptors when the endogenous dopamine levels are low.<unk> 's high selectivity towards D3 receptors could prove to reduce side effects associated with the other antipsychotic drugs, because D3 receptors are mainly located in the ventral striatum and would not incur the same motor side effects (extrapyramidal symptoms) as drugs that act on dorsal striatum dopamine receptors.<unk>  also acts on 5-HT1A receptors, though the affinity is considerably lower than the affinity to dopamine receptors (seen in monkey and rat brain studies). In the same studies,<unk>  has been noted to produce pro-cognitive effects, the mechanisms of which are currently under investigation. An example of pro-cognitive effects occurred in pre-clinical trials with rats: rats with<unk>  performed better in a scopolamine-induced learning impairment paradigm in a water labyrinth test. This may be due to the selective antagonist nature of D3 receptors, though further studies need to be conducted. This result could be very useful for schizophrenia, as one of the symptoms includes cognitive deficits.<unk>  has partial agonist as well as antagonist properties depending on the endogenous dopamine levels. When endogenous dopamine levels are high (as is hypothesized in schizophrenic patients),<unk>  acts as an antagonist by blocking dopamine receptors. When endogenous dopamine levels are low,<unk>  acts more as an agonist, increasing dopamine receptor activity. In monkey studies, the administration of increasing doses of<unk>  resulted in a dose-dependent and saturable reduction of specific binding. At the highest dose (300 μg/kg), the D2/D3 receptors were 94% occupied, while at the lowest dose (1 μg/kg), receptors were 5% occupied. Mechanism of<unk>  action as antagonist or agonist. Pharmacokinetics<unk>  has high oral bioavailability and can cross the blood brain barrier easily in humans because it is lipophilic. In rats, the oral bioavailability was 52% (with a dose of 1 mg/kg).<unk>  is metabolized primarily by the cytochrome P450 3A4 isoenzyme (CYP3A4), with some minor metabolism by CYP2D6.<unk>  does not induce the production of CYP3A4 or CYP1A2 in the liver, and weakly, competitively inhibits CYP2D6 and CYP3A4.
Cariprazine
Safrazine
Phendimetrazine
Pseudophenmetrazine
Meptazinol
Complanine
Bolesatine
Dotinurad