Clozapine (HF 1854) is a tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity.

M1 mAChR:9.5 nM(Ki), D2 Receptor:75 nM (Ki, antagonist), α2-adrenoceptor:51 nM (Ki, inhibitor), 5-HT2A receptor:4 nM (Ki, inhibitor), M4 mAChR:11 nM (EC50, agonist)

Clozapine significantly facilitated NMDA-evoked responses in a concentration-dependent manner (EC50: 14 nM).Clozapine produced excitatory postsynaptic potentials, which were blocked by glutamate receptor antagonists, suggesting that these excitatory postsynaptic potentials were the result of an increased release of excitatory amino acids.Clozapine is a full agonist at muscarinic M4 receptors, with an EC50=11 nM, and a -logEC50=6.52.The EC50=11 nM. Clozapine is a full agonist at muscarinic M4 receptors, with an EC50=11 nM, and inhibits forskolin-stimulated cAMP accumulation.Clozapine is a potent antagonist of agonist-induced responses at four other muscarinic receptor subtypes.

Clozapine significantly facilitated NMDA-evoked responses in a concentration-dependent manner (EC50: 14 nM).Clozapine produced excitatory postsynaptic potentials, which were blocked by glutamate receptor antagonists, suggesting that these excitatory postsynaptic potentials were the result of an increased release of excitatory amino acids.Clozapine is a full agonist at muscarinic M4 receptors, with an EC50=11 nM, and a -logEC50=6.52.The EC50=11 nM. Clozapine is a full agonist at muscarinic M4 receptors, with an EC50=11 nM, and inhibits forskolin-stimulated cAMP accumulation.Clozapine is a potent antagonist of agonist-induced responses at four other muscarinic receptor subtypes.