NAD-299 HCl | CAS#184674-99-5 | 5-HT1A receptor antagonist

MedKoo Cat#: 562977 | Name: NAD-299 HCl

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Description:

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

NAD-299 HCl is a high affinity 5-HT1A receptor antagonist.

Chemical Structure

NAD-299 HCl

CAS#184674-99-5

Theoretical Analysis

MedKoo Cat#: 562977

Name: NAD-299 HCl

CAS#: 184674-99-5

Chemical Formula: C18H24ClFN2O2

Exact Mass: 354.1510

Molecular Weight: 354.85

Elemental Analysis: C, 60.93; H, 6.82; Cl, 9.99; F, 5.35; N, 7.89; O, 9.02

Price and Availability

Size	Price	Availability	Quantity
10mg	USD 345.00	2 Weeks
50mg	USD 1,135.00	2 Weeks

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Synonym

NAD-299 HCl; NAD 299 HCl; NAD299 HCl; NAD-299 hydrochloride; NAD 299 Hydrochloride; NAD299 Hydrochloride;

IUPAC/Chemical Name

(R)-3-(dicyclobutylamino)-8-fluorochromane-5-carboxamide hydrochloride

InChi Key

GSZJANKLCPHEEX-BTQNPOSSSA-N

InChi Code

InChI=1S/C18H23FN2O2.ClH/c19-16-8-7-14(18(20)22)15-9-13(10-23-17(15)16)21(11-3-1-4-11)12-5-2-6-12;/h7-8,11-13H,1-6,9-10H2,(H2,20,22);1H/t13-;/m1./s1

SMILES Code

O=C(C1=C2C[C@@H](N(C3CCC3)C4CCC4)COC2=C(F)C=C1)N.[H]Cl

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:

NAD-299 HCl is a high affinity 5-HT1A receptor antagonist.

In vitro activity:

The only other receptors for which NAD-299 had affinity less than 1 microM were alpha-1 and beta adrenoceptors with Ki values of 260 and 340 nM, respectively. Thus, the selectivity of NAD-299 for 5-HT1A receptors was more than 400 times. Like WAY-100635, NAD-299 competitively blocked 5-HT-induced inhibition of vasoactive intestinal peptide-stimulated cAMP production in GH4ZD10 cells and had no intrinsic activity. Reference: J Pharmacol Exp Ther. 1997 Oct;283(1):216-25. https://pubmed.ncbi.nlm.nih.gov/9336327/

In vivo activity:

The effects of the HT(1A) receptor antagonist NAD-299 on extracellular acetylcholine (ACh) and glutamate (Glu) levels in the frontal cortex (FC) and ventral hippocampus (HPC) of the awake rats were investigated by the use of in vivo microdialysis. Systemic administration of NAD-299 (0.3; 1 and 3micromol/kg s.c.) caused a dose-dependent increase in ACh levels in FC and HPC (peak value of 209% and 221%, respectively) and this effect was comparable to that induced by donepezil (2.63micromol/kg s.c.). Reference: Eur Neuropsychopharmacol. 2010 Jul;20(7):487-500. https://pubmed.ncbi.nlm.nih.gov/20413275/

	Solvent	mg/mL	mM
Solubility
	DMSO	35.5	100.00
	Water	35.5	100.00

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 354.85 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.

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. Jerning E, Rosqvist S, Mohell N. Nad-299 antagonises 5-HT-stimulated and spiperone-inhibited [35S]GTPgammaS binding in cloned 5-HT1A receptors. J Recept Signal Transduct Res. 2002 Feb-Nov;22(1-4):483-95. doi: 10.1081/rrs-120014616. PMID: 12503636. 2. Johansson L, Sohn D, Thorberg SO, Jackson DM, Kelder D, Larsson LG, Rényi L, Ross SB, Wallsten C, Eriksson H, Hu PS, Jerning E, Mohell N, Westlind-Danielsson A. The pharmacological characterization of a novel selective 5-hydroxytryptamine1A receptor antagonist, NAD-299. J Pharmacol Exp Ther. 1997 Oct;283(1):216-25. PMID: 9336327. 3. Kehr J, Hu XJ, Yoshitake T, Wang FH, Osborne P, Stenfors C, Ogren SO. The selective 5-HT(1A) receptor antagonist NAD-299 increases acetylcholine release but not extracellular glutamate levels in the frontal cortex and hippocampus of awake rat. Eur Neuropsychopharmacol. 2010 Jul;20(7):487-500. doi: 10.1016/j.euroneuro.2010.03.003. Epub 2010 Apr 21. PMID: 20413275. 4. Pehrson R, Ojteg G, Ishizuka O, Andersson KE. Effects of NAD-299, a new, highly selective 5-HT1A receptor antagonist, on bladder function in rats. Naunyn Schmiedebergs Arch Pharmacol. 2002 Dec;366(6):528-36. doi: 10.1007/s00210-002-0650-y. Epub 2002 Oct 17. PMID: 12444493.

In vitro protocol:

In vivo protocol:

1. Kehr J, Hu XJ, Yoshitake T, Wang FH, Osborne P, Stenfors C, Ogren SO. The selective 5-HT(1A) receptor antagonist NAD-299 increases acetylcholine release but not extracellular glutamate levels in the frontal cortex and hippocampus of awake rat. Eur Neuropsychopharmacol. 2010 Jul;20(7):487-500. doi: 10.1016/j.euroneuro.2010.03.003. Epub 2010 Apr 21. PMID: 20413275. 2. Pehrson R, Ojteg G, Ishizuka O, Andersson KE. Effects of NAD-299, a new, highly selective 5-HT1A receptor antagonist, on bladder function in rats. Naunyn Schmiedebergs Arch Pharmacol. 2002 Dec;366(6):528-36. doi: 10.1007/s00210-002-0650-y. Epub 2002 Oct 17. PMID: 12444493.

1: Kumar JR, Rajkumar R, Lee LC, Dawe GS. Nucleus incertus contributes to an anxiogenic effect of buspirone in rats: Involvement of 5-HT1A receptors. Neuropharmacology. 2016 Nov;110(Pt A):1-14. doi: 10.1016/j.neuropharm.2016.07.019. Epub 2016 Jul 18. PubMed PMID: 27436722. 2: Pittalà V, Siracusa MA, Salerno L, Romeo G, Modica MN, Madjid N, Ogren SO. Analysis of mechanisms for memory enhancement using novel and potent 5-HT1A receptor ligands. Eur Neuropsychopharmacol. 2015 Aug;25(8):1314-23. doi: 10.1016/j.euroneuro.2015.04.017. Epub 2015 Apr 29. PubMed PMID: 25963581. 3: Dill MJ, Shaw J, Cramer J, Sindelar DK. 5-HT1A receptor antagonists reduce food intake and body weight by reducing total meals with no conditioned taste aversion. Pharmacol Biochem Behav. 2013 Nov;112:1-8. doi: 10.1016/j.pbb.2013.09.003. Epub 2013 Sep 21. PubMed PMID: 24064183. 4: Brenna E, Gatti FG, Malpezzi L, Monti D, Parmeggiani F, Sacchetti A. Synthesis of robalzotan, ebalzotan, and rotigotine precursors via the stereoselective multienzymatic cascade reduction of α,β-unsaturated aldehydes. J Org Chem. 2013 May 17;78(10):4811-22. doi: 10.1021/jo4003097. Epub 2013 May 8. PubMed PMID: 23611252. 5: Eriksson TM, Holst S, Stan TL, Hager T, Sjögren B, Ogren SÖ, Svenningsson P, Stiedl O. 5-HT1A and 5-HT7 receptor crosstalk in the regulation of emotional memory: implications for effects of selective serotonin reuptake inhibitors. Neuropharmacology. 2012 Nov;63(6):1150-60. doi: 10.1016/j.neuropharm.2012.06.061. Epub 2012 Jul 16. PubMed PMID: 22801295. 6: Wright JM, Dobosiewicz MR, Clarke PB. α- and β-Adrenergic receptors differentially modulate the emission of spontaneous and amphetamine-induced 50-kHz ultrasonic vocalizations in adult rats. Neuropsychopharmacology. 2012 Feb;37(3):808-21. doi: 10.1038/npp.2011.258. Epub 2011 Oct 26. PubMed PMID: 22030713; PubMed Central PMCID: PMC3260979. 7: Eriksson TM, Delagrange P, Spedding M, Popoli M, Mathé AA, Ögren SO, Svenningsson P. Emotional memory impairments in a genetic rat model of depression: involvement of 5-HT/MEK/Arc signaling in restoration. Mol Psychiatry. 2012 Feb;17(2):173-84. doi: 10.1038/mp.2010.131. Epub 2011 Jan 18. PubMed PMID: 21242991; PubMed Central PMCID: PMC3265836. 8: Kehr J, Hu XJ, Yoshitake T, Wang FH, Osborne P, Stenfors C, Ogren SO. The selective 5-HT(1A) receptor antagonist NAD-299 increases acetylcholine release but not extracellular glutamate levels in the frontal cortex and hippocampus of awake rat. Eur Neuropsychopharmacol. 2010 Jul;20(7):487-500. doi: 10.1016/j.euroneuro.2010.03.003. Epub 2010 Apr 21. PubMed PMID: 20413275. 9: Youn J, Misane I, Eriksson TM, Millan MJ, Ogren SO, Verhage M, Stiedl O. Bidirectional modulation of classical fear conditioning in mice by 5-HT(1A) receptor ligands with contrasting intrinsic activities. Neuropharmacology. 2009 Oct-Nov;57(5-6):567-76. doi: 10.1016/j.neuropharm.2009.07.011. Epub 2009 Jul 15. PubMed PMID: 19607850. 10: Lindström E, Ravnefjord A, Brusberg M, Hjorth S, Larsson H, Martinez V. The selective 5-hydroxytryptamine 1A antagonist, AZD7371 [3(R)-(N,N-dicyclobutylamino)-8-fluoro-3,4-dihydro-2H-1-benzopyran-5-carboxamide (R,R)-tartrate monohydrate] (robalzotan tartrate monohydrate), inhibits visceral pain-related visceromotor, but not autonomic cardiovascular, responses to colorectal distension in rats. J Pharmacol Exp Ther. 2009 Jun;329(3):1048-55. doi: 10.1124/jpet.109.152330. Epub 2009 Mar 26. PubMed PMID: 19325032. 11: Drossman DA, Danilewitz M, Naesdal J, Hwang C, Adler J, Silberg DG. Randomized, double-blind, placebo-controlled trial of the 5-HT1A receptor antagonist AZD7371 tartrate monohydrate (robalzotan tartrate monohydrate) in patients with irritable bowel syndrome. Am J Gastroenterol. 2008 Oct;103(10):2562-9. doi: 10.1111/j.1572-0241.2008.02115.x. Epub 2008 Sep 4. PubMed PMID: 18775020. 12: Madjid N, Tottie EE, Lüttgen M, Meister B, Sandin J, Kuzmin A, Stiedl O, Ogren SO. 5-Hydroxytryptamine 1A receptor blockade facilitates aversive learning in mice: interactions with cholinergic and glutamatergic mechanisms. J Pharmacol Exp Ther. 2006 Feb;316(2):581-91. Epub 2005 Oct 13. PubMed PMID: 16223872. 13: Eriksson MA, Gabrielsson J, Nilsson LB. Studies of drug binding to plasma proteins using a variant of equilibrium dialysis. J Pharm Biomed Anal. 2005 Jul 1;38(3):381-9. Epub 2005 Feb 24. PubMed PMID: 15925237. 14: Lüttgen M, Elvander E, Madjid N, Ogren SO. Analysis of the role of 5-HT1A receptors in spatial and aversive learning in the rat. Neuropharmacology. 2005 May;48(6):830-52. PubMed PMID: 15829255. 15: Hajós M, Gartside SE, Varga V, Sharp T. In vivo inhibition of neuronal activity in the rat ventromedial prefrontal cortex by midbrain-raphe nuclei: role of 5-HT1A receptors. Neuropharmacology. 2003 Jul;45(1):72-81. PubMed PMID: 12814660. 16: Tordera R, Pei Q, Newson M, Gray K, Sprakes M, Sharp T. Effect of different 5-HT1A receptor antagonists in combination with paroxetine on expression of the immediate-early gene Arc in rat brain. Neuropharmacology. 2003 Jun;44(7):893-902. PubMed PMID: 12726821. 17: Andrée B, Hedman A, Thorberg SO, Nilsson D, Halldin C, Farde L. Positron emission tomographic analysis of dose-dependent NAD-299 binding to 5-hydroxytryptamine-1A receptors in the human brain. Psychopharmacology (Berl). 2003 Apr;167(1):37-45. Epub 2003 Mar 11. PubMed PMID: 12632244. 18: Misane I, Ogren SO. Selective 5-HT1A antagonists WAY 100635 and NAD-299 attenuate the impairment of passive avoidance caused by scopolamine in the rat. Neuropsychopharmacology. 2003 Feb;28(2):253-64. PubMed PMID: 12589378. 19: Jerning E, Rosqvist S, Mohell N. Nad-299 antagonises 5-HT-stimulated and spiperone-inhibited [35S]GTPgammaS binding in cloned 5-HT1A receptors. J Recept Signal Transduct Res. 2002 Feb-Nov;22(1-4):483-95. PubMed PMID: 12503636. 20: Pehrson R, Ojteg G, Ishizuka O, Andersson KE. Effects of NAD-299, a new, highly selective 5-HT1A receptor antagonist, on bladder function in rats. Naunyn Schmiedebergs Arch Pharmacol. 2002 Dec;366(6):528-36. Epub 2002 Oct 17. PubMed PMID: 12444493.