LOXITANE C

Names

[ Name ]:
LOXITANE C

[Synonym ]:
2-Chloro-11-(4-methyl-1-piperazinyl)dibenz[b,f][1,4]oxazepine Monohydrochloride
Desconex (TN)
Dibenz[b,f][1,4]oxazepine, 2-chloro-11-(4-methyl-1-piperazinyl)-, hydrochloride (1:1)
LOXITANE C
2-Chloro-11-(4-methyl-1-piperazinyl)dibenzo[b,f][1,4]oxazepine hydrochloride (1:1)
Dibenz(b,f)(1,4)oxazepine,2-chloro-11-(4-methyl-1-piperazinyl)-,monohydrochloride
Loxapine hydrochloride
Loxapine monohydrochloride
2-Chloro-11-(4-methyl-1-piperazinyl)dibenz(b,f)(1,4)oxazepine monohydrochloride
Loxapine HCl

Biological Activity

[Description]:

Loxapine hydrochloride is an orally active dopamine inhibitor, 5-HT receptor antagonist and also a dibenzoxazepine anti-psychotic agent[1][4].

[Related Catalog]:

Signaling Pathways >> GPCR/G Protein >> Dopamine Receptor

Signaling Pathways >> Neuronal Signaling >> Dopamine Receptor

Research Areas >> Neurological Disease

Signaling Pathways >> GPCR/G Protein >> 5-HT Receptor

Signaling Pathways >> Neuronal Signaling >> 5-HT Receptor

[Target]

human 5-HT2

Human D4 Receptor

Human D1 Receptor

Human D2 Receptor

[In Vitro]

In the presence of Loxapine, [3H]ketanserin binds to 5-HT2 receptor in Frontal cortex of brain in human and bovine with Ki 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[1]. 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[2].

[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[3]. Animal Model: Adult male Wistar rats (150-175 g)[3] Dosage: 5 mg/kg Administration: Intraperitoneal injection, daily for 4 or 10 weeks Result: Induced a very significant reduction (more than 50%) of serotonin (S2) receptor density after 4 weeks or 10 weeks of daily injection, but did not produce any significant increase in dopamine receptor density.

[References]

[1]. Singh AN, et al. A neurochemical basis for the antipsychotic activity of loxapine: interactions with dopamine D1, D2, D4 and serotonin 5-HT2 receptor subtypes. J Psychiatry Neurosci. 1996 Jan;21(1):29-35.

[2]. Labuzek K, et al. Chlorpromazine and loxapine reduce interleukin-1beta and interleukin-2 release by rat mixed glial and microglial cell cultures. Eur Neuropsychopharmacol. 2005 Jan;15(1):23-30.

[3]. Lee T, et al. Loxapine and clozapine decrease serotonin (S2) but do not elevate dopamine (D2) receptor numbers in the rat brain. Psychiatry Res. 1984 Aug;12(4):277-85.

[4]. Keating GM. Loxapine inhalation powder: a review of its use in the acute treatment of agitation in patients with bipolar disorder or schizophrenia. CNS Drugs. 2013 Jun;27(6):479-89.