DHA-clozapine

DHA-clozapine

Systematic (IUPAC) name
(4Z,7Z,10Z,13Z,16Z,19Z)-1-[3-chloro-6-(4-methylpiperazin-1-yl)benzo[b][1,4]benzodiazepin-11-yl]docosa-4,7,10,13,16,19-hexaen-1-one
Clinical data
Trade names	Clozaprexin
Legal status	Investigational New Medicine
Identifiers
CAS Number	225916-82-5
ATC code	none
PubChem	CID 9852332
ChemSpider	8028044
Synonyms	Docosahexaenoyl clozapine
Chemical data
Formula	C40H49ClN4O
Molar mass	637.30 g/mol
SMILES Clc1ccc2N(C(=O)CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CC)c4ccccc4C(=N/c2c1)\N3CCN(C)CC3
InChI InChI=1S/C40H49ClN4O/c1-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-20-21-26-39(46)45-37-25-23-22-24-35(37)40(44-31-29-43(2)30-32-44)42-36-33-34(41)27-28-38(36)45/h4-5,7-8,10-11,13-14,16-17,19-20,22-25,27-28,33H,3,6,9,12,15,18,21,26,29-32H2,1-2H3/b5-4-,8-7-,11-10-,14-13-,17-16-,20-19- Key:RPSJOJIGGSRDMO-JDPCYWKWSA-N
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DHA-clozapine (tentative trade name Clozaprexin) is an atypical antipsychotic that has been developed by Protarga.^[1] The drug has been created by the association of the fatty acid docosahexaenoic acid (DHA) with clozapine. The advantages of this drug are that until the DHA and clozapine are separated, the drug is inactive; once it penetrates the blood–brain barrier, the DHA and clozapine are freed from each other slowly by enzymatic activity and therefore more clozapine is liberated where it is needed, rendering the drug much more potent, actively longer in duration, and therefore requiring a much lower dosage, which results in fewer side effects.^[2] Development of the drug has been discontinued as of 2007.

Motives for creation

In controlled studies, clozapine was more effective than competing atypical antipsychotics. Clozapine also lowers patients' risk of suicide. Both of these qualities distinguish it from almost all other atypicals. But clozapine also causes significant amounts of low blood pressure, body weight increases, type II diabetes, and agranulocytosis. It was believed that, insofar as the above side effects are caused by the presence of active clozapine outside the brain, molecular attachment to DHA might reduce their frequency by passivating the form in which the drug exists prior to crossing the blood–brain barrier.^[2]

References

1. Preclinical Data on Novel Antipsychotic Agent, Harvard Medical School Investigators Report
2. Baldessarini, R.; Campbell, A.; Webb, N. L.; Swindell, C. S.; Flood, J. G.; Shashoua, V. E.; Kula, N. S.; Hemamalini, S.; Bradley, M. O. (2001). "Fatty Acid Derivatives of Clozapine Prolonged Antidopaminergic Activity of Docosahexaenoylclozapine in the Rat". Neuropsychopharmacology 24 (1): 55–65. doi:10.1016/S0893-133X(00)00173-1. PMID 11106876.