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MedKoo Cat#: 328095 | Name: Norclozapine
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Norclozapine, also known as ACP-104, is a 5-HT2A inverse/dopamine/muscarinic receptor agonist potentially for the treatment of schizophrenia.

Chemical Structure

Norclozapine
Norclozapine
CAS#6104-71-8

Theoretical Analysis

MedKoo Cat#: 328095

Name: Norclozapine

CAS#: 6104-71-8

Chemical Formula: C17H17ClN4

Exact Mass: 312.1142

Molecular Weight: 312.80

Elemental Analysis: C, 65.28; H, 5.48; Cl, 11.33; N, 17.91

Price and Availability

Size Price Availability Quantity
5mg USD 300.00 2 weeks
10mg USD 550.00 2 weeks
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Related CAS #
No Data
Synonym
Norclozapine; ACP-104; ACP104; ACP 104; N-Desmethylclozapine; Demethylclozapine.
IUPAC/Chemical Name
8-Chloro-11-(1-piperazinyl)-5H-dibenzo(b,e)(1,4)diazepine
InChi Key
JNNOSTQEZICQQP-UHFFFAOYSA-N
InChi Code
InChI=1S/C17H17ClN4/c18-12-5-6-15-16(11-12)21-17(22-9-7-19-8-10-22)13-3-1-2-4-14(13)20-15/h1-6,11,19-20H,7-10H2
SMILES Code
ClC1=CC=C2C(N=C(N3CCNCC3)C4=CC=CC=C4N2)=C1
Appearance
Solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Product Data
Product Data
Instruction
View handling instruction
Biological target:
N-Desmethylclozapine is a potent, allosteric and partial M1 receptors agonist (EC50=115 nM) and is able to potentiate hippocampal N-methyl-d-aspartate (NMDA) receptor currents through M1 receptor activation. N-Desmethylclozapine is also a δ-opioid agonist.
In vitro activity:
Clozapine and N-desmethylclozapine antagonized 5-HT-stimulated phosphoinositide hydrolysis with IC50 values of 110 and 29.4 nM, respectively. In conclusion, this study demonstrates that clozapine and one of its major metabolites in man, N-desmethylclozapine, are potent 5-HT1C receptor antagonists. Reference: Eur J Pharmacol. 1993 Apr 15;245(2):179-82. https://pubmed.ncbi.nlm.nih.gov/8387927/
In vivo activity:
NDMC (3mg/kg) and clozapine (1-3mg/kg) each improved the reduction of social interaction caused by a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist, 5R,10S-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801) (0.1mg/kg), without affecting locomotor activity in rats. NDMC (3-10mg/kg) and clozapine (1-3mg/kg) each also resulted in better discrimination of a novel from a familiar object 24h after a training trial in a rat object recognition test. Reference: Brain Res Bull. 2011 Oct 10;86(3-4):146-51. https://pubmed.ncbi.nlm.nih.gov/21855612/
Solvent mg/mL mM
Solubility
DMF 10.0 31.97
DMSO 30.0 95.91
DMSO:PBS (pH 7.2) (1:1) 0.5 1.60
Ethanol 5.0 15.98
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 312.80 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Thomas DR, Dada A, Jones GA, Deisz RA, Gigout S, Langmead CJ, Werry TD, Hendry N, Hagan JJ, Davies CH, Watson JM. N-desmethylclozapine (NDMC) is an antagonist at the human native muscarinic M(1) receptor. Neuropharmacology. 2010 Jun;58(8):1206-14. doi: 10.1016/j.neuropharm.2010.02.017. Epub 2010 Mar 3. PMID: 20206188. 2. Kuoppamäki M, Syvälahti E, Hietala J. Clozapine and N-desmethylclozapine are potent 5-HT1C receptor antagonists. Eur J Pharmacol. 1993 Apr 15;245(2):179-82. doi: 10.1016/0922-4106(93)90126-t. PMID: 8387927. 3. Maehara S, Okuda S, Ohta H. Ameliorative effect of N-desmethylclozapine in animal models of social deficits and cognitive functions. Brain Res Bull. 2011 Oct 10;86(3-4):146-51. doi: 10.1016/j.brainresbull.2011.08.004. Epub 2011 Aug 9. PMID: 21855612. 4. Ekström J, Godoy T, Riva A. N-Desmethylclozapine exerts dual and opposite effects on salivary secretion in the rat. Eur J Oral Sci. 2010 Feb;118(1):1-8. doi: 10.1111/j.1600-0722.2009.00696.x. PMID: 20156258.
In vitro protocol:
1. Thomas DR, Dada A, Jones GA, Deisz RA, Gigout S, Langmead CJ, Werry TD, Hendry N, Hagan JJ, Davies CH, Watson JM. N-desmethylclozapine (NDMC) is an antagonist at the human native muscarinic M(1) receptor. Neuropharmacology. 2010 Jun;58(8):1206-14. doi: 10.1016/j.neuropharm.2010.02.017. Epub 2010 Mar 3. PMID: 20206188. 2. Kuoppamäki M, Syvälahti E, Hietala J. Clozapine and N-desmethylclozapine are potent 5-HT1C receptor antagonists. Eur J Pharmacol. 1993 Apr 15;245(2):179-82. doi: 10.1016/0922-4106(93)90126-t. PMID: 8387927.
In vivo protocol:
1. Maehara S, Okuda S, Ohta H. Ameliorative effect of N-desmethylclozapine in animal models of social deficits and cognitive functions. Brain Res Bull. 2011 Oct 10;86(3-4):146-51. doi: 10.1016/j.brainresbull.2011.08.004. Epub 2011 Aug 9. PMID: 21855612. 2. Ekström J, Godoy T, Riva A. N-Desmethylclozapine exerts dual and opposite effects on salivary secretion in the rat. Eur J Oral Sci. 2010 Feb;118(1):1-8. doi: 10.1111/j.1600-0722.2009.00696.x. PMID: 20156258.
1: Anderson SG, Livingston M, Couchman L, Smith DJ, Connolly M, Miller J, Flanagan RJ, Heald AH. Sex differences in plasma clozapine and norclozapine concentrations in clinical practice and in relation to body mass index and plasma glucose concentrations: a retrospective survey. Ann Gen Psychiatry. 2015 Nov 14;14:39. doi: 10.1186/s12991-015-0075-x. PubMed PMID: 26583040; PubMed Central PMCID: PMC4650861. 2: Couchman L, Subramaniam K, Fisher DS, Belsey SL, Handley SA, Flanagan RJ. Automated Analysis of Clozapine and Norclozapine in Human Plasma Using Novel Extraction Plate Technology and Flow-Injection Tandem Mass Spectrometry. Ther Drug Monit. 2016 Feb;38(1):42-9. doi: 10.1097/FTD.0000000000000231. PubMed PMID: 26349082. 3: Patteet L, Maudens KE, Vermeulen Z, Dockx G, De Doncker M, Morrens M, Sabbe B, Neels H. Retrospective evaluation of therapeutic drug monitoring of clozapine and norclozapine in Belgium using a multidrug UHPLC-MS/MS method. Clin Biochem. 2014 Dec;47(18):336-9. doi: 10.1016/j.clinbiochem.2014.09.021. PubMed PMID: 25289972. 4: Li CH, Stratford RE Jr, Velez de Mendizabal N, Cremers TI, Pollock BG, Mulsant BH, Remington G, Bies RR. Prediction of brain clozapine and norclozapine concentrations in humans from a scaled pharmacokinetic model for rat brain and plasma pharmacokinetics. J Transl Med. 2014 Aug 20;12:203. doi: 10.1186/1479-5876-12-203. PubMed PMID: 25142323; PubMed Central PMCID: PMC4261612. 5: Couchman L, Belsey SL, Handley SA, Flanagan RJ. A novel approach to quantitative LC-MS/MS: therapeutic drug monitoring of clozapine and norclozapine using isotopic internal calibration. Anal Bioanal Chem. 2013 Nov;405(29):9455-66. doi: 10.1007/s00216-013-7361-8. PubMed PMID: 24091736. 6: Légaré N, Grégoire CA, De Benedictis L, Dumais A. Increasing the clozapine: norclozapine ratio with co-administration of fluvoxamine to enhance efficacy and minimize side effects of clozapine therapy. Med Hypotheses. 2013 Jun;80(6):689-91. doi: 10.1016/j.mehy.2012.12.024. PubMed PMID: 23490199. 7: Li LJ, Shang DW, Li WB, Guo W, Wang XP, Ren YP, Li AN, Fu PX, Ji SM, Lu W, Wang CY. Population pharmacokinetics of clozapine and its primary metabolite norclozapine in Chinese patients with schizophrenia. Acta Pharmacol Sin. 2012 Nov;33(11):1409-16. doi: 10.1038/aps.2012.71. PubMed PMID: 22820910; PubMed Central PMCID: PMC4011352. 8: Couchman L, Bowskill SV, Handley S, Patel MX, Flanagan RJ. Plasma clozapine and norclozapine in relation to prescribed dose and other factors in patients aged <18 years: data from a therapeutic drug monitoring service, 1994-2010. Early Interv Psychiatry. 2013 May;7(2):122-30. doi: 10.1111/j.1751-7893.2012.00374.x. PubMed PMID: 22747759. 9: Bowskill S, Couchman L, MacCabe JH, Flanagan RJ. Plasma clozapine and norclozapine in relation to prescribed dose and other factors in patients aged 65 years and over: data from a therapeutic drug monitoring service, 1996-2010. Hum Psychopharmacol. 2012 May;27(3):277-83. doi: 10.1002/hup.2223. PubMed PMID: 22419536. 10: González-Esquivel DF, Castro N, Ramírez-Bermúdez J, Custodio V, Rojas-Tomé S, Castro-Román R, Jung-Cook H. Plasma levels of clozapine and norclozapine in Mexican schizophrenia patients. Arzneimittelforschung. 2011;61(6):335-9. doi: 10.1055/s-0031-1296207. PubMed PMID: 21827043. 11: Wohlfarth A, Toepfner N, Hermanns-Clausen M, Auwärter V. Sensitive quantification of clozapine and its main metabolites norclozapine and clozapine-N-oxide in serum and urine using LC-MS/MS after simple liquid-liquid extraction work-up. Anal Bioanal Chem. 2011 May;400(3):737-46. doi: 10.1007/s00216-011-4831-8. PubMed PMID: 21394453. 12: Murayama-Sung L, Ahmed I, Goebert D, Alaimalo E, Sung H. The impact of hospital smoking ban on clozapine and norclozapine levels. J Clin Psychopharmacol. 2011 Feb;31(1):124-6. doi: 10.1097/JCP.0b013e318206bdcd. PubMed PMID: 21192157. 13: Couchman L, Morgan PE, Spencer EP, Johnston A, Flanagan RJ. Plasma clozapine and norclozapine in patients prescribed different brands of clozapine (Clozaril, Denzapine, and Zaponex). Ther Drug Monit. 2010 Oct;32(5):624-7. doi: 10.1097/FTD.0b013e3181f0a1a2. PubMed PMID: 20720516. 14: Vardakou I, Dona A, Pistos C, Alevisopoulos G, Athanaselis S, Maravelias C, Spiliopoulou C. Validated GC/MS method for the simultaneous determination of clozapine and norclozapine in human plasma. Application in psychiatric patients under clozapine treatment. J Chromatogr B Analyt Technol Biomed Life Sci. 2010 Sep 1;878(25):2327-32. doi: 10.1016/j.jchromb.2010.07.001. PubMed PMID: 20674521. 15: Couchman L, Morgan PE, Spencer EP, Flanagan RJ. Plasma clozapine, norclozapine, and the clozapine:norclozapine ratio in relation to prescribed dose and other factors: data from a therapeutic drug monitoring service, 1993-2007. Ther Drug Monit. 2010 Aug;32(4):438-47. doi: 10.1097/FTD.0b013e3181dad1fb. PubMed PMID: 20463634. 16: Gershkovich P, Sivak O, Sharma A, Barr AM, Procyshyn R, Wasan KM. Effect of hypertriglyceridemia on the pharmacokinetics and blood-brain barrier penetration of clozapine and norclozapine following administration to rats. Eur Neuropsychopharmacol. 2010 Aug;20(8):545-52. doi: 10.1016/j.euroneuro.2010.01.002. PubMed PMID: 20163937. 17: Rao LV, Snyder ML, Vallaro GM. Rapid liquid chromatography/tandem mass spectrometer (LCMS) method for clozapine and its metabolite N-desmethyl clozapine (norclozapine) in human serum. J Clin Lab Anal. 2009;23(6):394-8. doi: 10.1002/jcla.20345. PubMed PMID: 19927349. 18: Ming DS, Heathcote J. Therapeutic drug monitoring of clozapine and norclozapine in human serum using ultra-performance liquid chromatography- tandem mass spectrometry. J Anal Toxicol. 2009 May;33(4):198-203. PubMed PMID: 19470221. 19: Lee ST, Ryu S, Nam HJ, Lee SY, Hong KS. Determination of pharmacokinetic properties of clozapine and norclozapine in Korean schizophrenia patients. Int Clin Psychopharmacol. 2009 May;24(3):139-44. doi: 10.1097/YIC.0b013e3283277627. PubMed PMID: 19194306. 20: Guitton C, Kinowski JM, Gomeni R, Bressolle F. A Kinetic Model for Simultaneous Fit of Clozapine and Norclozapine Concentrations in Chronic Schizophrenic Patients during Long-Term Treatment. Clin Drug Investig. 1998;16(1):35-43. PubMed PMID: 18370516.