Pharmacodynamics + Protein Ki () Ki () 5-HT1A 123.7 13.9 5-HT1B 519 406.8 5-HT1D 1,356 476.2 5-HT2A 5.35 10.9 5-HT2B 8.37 2.8 5-HT2C 9.44 11.9 5-HT3 241 272.2 5-HT5A 3,857 350.6 5-HT6 13.49 11.6 5-HT7 17.95 60.1 α1A 1.62 104.8 α1B 7 85.2 α2A 37 137.6 α2B 26.5 95.1 α2C 6 117.7 β1 5,000 6,239 β2 1,650 4,725 D1 266.25 14.3 D2 157 101.4 D3 269.08 193.5 D4 26.36 63.94 D5 255.33 283.6 H1 1.13 3.4 H2 153 345.1 H3 >10,000 >10,000 H4 665 1,028 M1 6.17 67.6 M2 36.67 414.5 M3 19.25 95.7 M4 15.33 169.9 M5 15.5 35.4 1,624 316.6 3,168 493.9 >10,000 >10,000 The smaller the value, the more strongly the drug binds to the site. All data are for cloned human proteins.<unk>  is classified as an atypical antipsychotic drug because it binds to serotonin as well as dopamine receptors.<unk>  is an antagonist at the 5-HT2A subunit of the serotonin receptor, putatively improving depression, anxiety, and the negative cognitive symptoms associated with schizophrenia. A direct interaction of<unk>  with the GABAB receptor has also been shown. GABAB receptor-deficient mice exhibit increased extracellular dopamine levels and altered locomotor behaviour equivalent to that in schizophrenia animal models. GABAB receptor agonists and positive allosteric modulators reduce the locomotor changes in these models.<unk>  induces the release of glutamate and D-serine, an agonist at the glycine site of the NMDA receptor, from astrocytes, and reduces the expression of astrocytic glutamate transporters. These are direct effects that are also present in astrocyte cell cultures not containing neurons.<unk>  prevents impaired NMDA receptor expression caused by NMDA receptor antagonists. Pharmacokinetics N-desmethylclozapine (norclozapine),<unk> 's major active metabolite. The absorption of<unk>  is almost complete following oral administration, but the oral bioavailability is only 60 to 70% due to first-pass metabolism. The time to peak concentration after oral dosing is about 2.5 hours, and food does not appear to affect the bioavailability of<unk> . However, it was shown that co-administration of food decreases the rate of absorption. The elimination half-life of<unk>  is about 14 hours at steady state conditions (varying with daily dose).<unk>  is extensively metabolized in the liver, via the cytochrome P450 system, to polar metabolites suitable for elimination in the urine and feces. The major metabolite, norclozapine (desmethyl-clozapine), is pharmacologically active. The cytochrome P450 isoenzyme 1A2 is primarily responsible for<unk>  metabolism, but 2C, 2D6, 2E1 and 3A3/4 appear to play roles as well. Agents that induce (e.g., cigarette smoke) or inhibit (e.g., theophylline, ciprofloxacin, fluvoxamine) CYP1A2 may increase or decrease, respectively, the metabolism of<unk> . For example, the induction of metabolism caused by smoking means that smokers require up to double the dose of<unk>  compared with non-smokers to achieve an equivalent plasma concentration.<unk>  and norclozapine (desmethyl-clozapine) plasma levels may also be monitored, though they show a significant degree of variation and are higher in women and increase with age. Monitoring of plasma levels of<unk>  and norclozapine has been shown to be useful in assessment of compliance, metabolic status, prevention of toxicity, and in dose optimisation.
Clozapine
Desmethylclozapine
Chlorpromazine
Ziprasidone
Aripiprazole
Lorpiprazole
Risperidone
Chlortalidone