Clozapine-d4

Clozapine-d₄ is intended for use as an internal standard for the quantification of clozapine by GC- or LC-MS. Clozapine is a partial agonist at the serotonin (5-HT) receptor subtype 5-HT_1A (K_i = 180 nM).^1,2 It also binds to 5-HT_2A, 5-HT_2C, 5-HT₃, 5-HT₆ and 5-HT₇ receptors (K_is = 3.3, 13, 110, 4, and 21 nM, respectively), as well as the histamine H₁ and α₁-adrenergic receptors (K_is = 2.1 and 23 nM, respectively). It does not bind to the 5-HT_1B receptor and has a lower affinity for dopamine receptors (K_is = 540, 150, and 360 nM for D_1-3, respectively). Clozapine 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.³ It reverses locomotor hyperactivity and deficits in prepulse inhibition of acoustic startle in a rat neonatal ventral hippocampal ibotenic lesion model of schizophrenia when administered at a dose of 2.5 mg/kg per day.⁴ Formulations containing clozapine have been used in the treatment of schizophrenia.

1.Millan, M.J.Improving the treatment of Schizophrenia: Focus on serotonin (5-HT)1A receptorsJ. Pharmacol. Exp. Ther.295(3)853-861(2000) 2.Schotte, A., Janssen, P.F., Gommeren, W., et al.Risperidone compared with new and reference antipsychotic drugs: In vitro and in vivo receptor bindingPsychopharmacology (Berl)124(1-2)57-73(1996) 3.Tanahashi, S., Yamamura, S., Nakagawa, M., et al.Clozapine, but not haloperidol, enhances glial D-serin and L-glutamate release in rat frontal cortex and primary cultured astrocytesBr. J. Pharmacol.1651543-1555(2012) 4.Rueter, L.E., Ballard, M.E., Gallagher, K.B., et al.Chronic low dose risperidone and clozapine alleviate positive but not negative symptoms in the rat neonatal ventral hippocampal lesion model of schizophreniaPsychopharmacology (Berl).176(3-4)312-319(2004)