Harman-d3 is a deuterated version of Harmane. Harmane is a benzodiazepine receptor inhibitor (IC50=7 μM), with IC50 of 24 μM, 2.8 μM, 0.5 μM, 5 μM and 18 μM for mACh, Opioid Receptor, MAO-A/B and α2-adrenergic receptor, respectively. Harmane also inhibits spiropyridinol and serotonin with IC50 of 163 μM and 101 μM, respectively. Harmane inhibits I1 imidazoline receptors (IC50 = 30 nM) to lower blood pressure and has antidepressant, anxiolytic, anticonvulsant and analgesic effects. Harmane inhibits dopamine biosynthesis by reducing tyrosine hydroxylase (TH) activity and enhancing L-DOPA-induced PC12 cell toxicity. Harmane also enhances 2-acetylaminofluorene (AAF)-induced mutagenicity.

Physicochemical Properties

Molecular Formula	C12H7D3N2
Molecular Weight	185.24
CAS #	1216708-84-7
Related CAS #	Harmane;486-84-0
PubChem CID	46781679
Appearance	Typically exists as solids at room temperature
LogP	3.025
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	1
Heavy Atom Count	14
Complexity	216
Defined Atom Stereocenter Count	0
SMILES	CC1=NC=CC2=C1NC3=CC=CC=C23
Synonyms	Harmanine-d3
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

References

[1]. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019 Feb;53(2):211-216. [2]. On the neuropharmacology of Harmane and other beta-carbolines. Pharmacol Biochem Behav. 1981 May;14(5):693-9. [3]. Harmane produces hypotension following microinjection into the RVLM: possible role of I(1)-imidazoline receptors. Br J Pharmacol. 2000 Mar;129(6):1057-9. [4]. β-Carbolines as selective monoamine oxidase inhibitors:In vivo implications. [5]. Comutagenic effect of norharman and harman with 2-acetylaminofluorene derivatives. Proc Natl Acad Sci U S A. 1978 Feb;75(2):928-30. [6]. Harmane induces anxiolysis and antidepressant-like effects in rats. Ann N Y Acad Sci. 2005 Aug 9;65(3):391-6. [7]. Effects of harman and norharman on dopamine biosynthesis and L-DOPA-induced cytotoxicity in PC12 cells. Eur J Pharmacol. 2008 Jun 10;587(1-3):57-64.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	5.3984 mL	26.9920 mL	53.9840 mL
	5 mM	1.0797 mL	5.3984 mL	10.7968 mL
	10 mM	0.5398 mL	2.6992 mL	5.3984 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.