Dopamine Receptors are a class of G protein-coupled receptors that are prominent in the vertebrate central nervous system (CNS). The neurotransmitter dopamine is the primary endogenous ligand for dopamine receptors. Abnormal dopamine receptor signaling and dopaminergic nerve function is implicated in several neuropsychiatric disorders. Thus, dopamine receptors are common neurologic drug targets. Antipsychotics are often dopamine receptor antagonists while psychostimulants are typically indirect agonists of dopamine receptors. There are at least five subtypes of dopamine receptors, D1, D2, D3, D4, and D5.

5-HT receptors (Serotonin receptors) are a group of G protein-coupled receptors (GPCRs) and ligand-gated ion channels (LGICs) found in the central and peripheral nervous systems. They mediate both excitatory and inhibitory neurotransmission. And they modulate the release of many neurotransmitters, as well as many hormones. The serotonin receptors influence various biological and neurological processes. The serotonin receptors are the target of a variety of pharmaceutical drugs.

Loxapine is an Orally active dopamine inhibitor and 5-HT2A Receptor Antagonist for Schizophrenia Research

Loxapine is an orally active dopamine inhibitor and 5-HT receptor antagonist. What’s more, Loxapine can be used as a dibenzoxazepine anti-psychotic agent.

In Vitro, In the presence of Loxapine, [³H]ketanserin binds to 5-HT2 receptor in Frontal cortex of brain in human and bovine with K_i value of 6.2 nM and 6.6 nM, respectively. Loxapine has the rank order of potency for the various receptors appears to be as follows: 5-HT2≥D4>>>D1>D2 in comparing competition experiments involving the human membranes. Moreover, Loxapine (0-20 μM, 24 h or 72 h) reduces IL-1β secretion by LPS-activated mixed glia cultures, reduces IL-2 secretion in mixed glia cultures, and decreases IL-1β and IL-2 secretion in LPS-induced microglia cultures. In Vivo, Loxapine (5 mg/kg; i.p.; daily for 4 or 10 weeks) decreases serotonin (S2) but does not elevate dopamine (D2) receptor numbers in the rat brain.

In conclusion, Loxapine is an orally active dopamine inhibitor and 5-HT receptor antagonist for psychosis.

Reference:

[1]. J Psychiatry Neurosci. 1996 Jan;21(1):29-35.

[2]. Eur Neuropsychopharmacol. 2005 Jan;15(1):23-30.

[3]. Psychiatry Res. 1984 Aug;12(4):277-85.