Synonym
MK912; MK 912; MK-912
IUPAC/Chemical Name
(2S,12bS)-1',3'-dimethyl-1,3,4,5',6,6',7,12b-octahydro-1'H-spiro[benzofuro[2,3-a]quinolizine-2,4'-pyrimidin]-2'(3'H)-one hydrochloride
InChi Key
ALYCEQJIRFYVGE-VASSOYJASA-N
InChi Code
InChI=1S/C20H25N3O2.ClH/c1-21-11-8-20(22(2)19(21)24)9-12-23-10-7-15-14-5-3-4-6-17(14)25-18(15)16(23)13-20;/h3-6,16H,7-13H2,1-2H3;1H/t16-,20+;/m0./s1
SMILES Code
O=C1N(C)[C@]2(CCN1C)CCN3CCC4=C(OC5=CC=CC=C54)[C@]3([H])C2.[H]Cl
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, not in water
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
Biological target:
MK-912 is a potent new selective alpha 2-adrenergic receptor antagonist.
In vitro activity:
Here, 3 H-rauwolscine whole cell binding was used to determine the affinity and selectivity of 99 α-antagonists (including antidepressants and antipsychotics) in CHO cells expressing human α2A, α2B, or α2C-adrenoceptors, using an identical method to β and α1-adrenoceptor measurements, thus allowing direct human receptor comparisons. MK-912 is the highest-affinity, most α2C-selective antagonist (0.15 nM α2C-affinity) although its α2C-selectivity is only 13-fold greater than at α2A.
Reference: Pharmacol Res Perspect. 2022 Apr;10(2):e00936. https://pubmed.ncbi.nlm.nih.gov/35224877/
In vivo activity:
Male diabetic db/db and control C57BL/6J mice, anaesthetized with pentobarbitone, were treated with tetrodotoxin for eliminating the sympathetic nerve tone and artificially ventilated. Cooling the air temperature around the foot reduced PSBF in a temperature-dependent manner in control and db/db mice. Phentolamine, a non-selective α-antagonist, bunazosin, a selective α1-antagonist, MK-912, a selective α2C-antagonist, and Y-27632, a Rho-kinase inhibitor, significantly inhibited the PSBF reduction induced by cooling to 15 °C in both mice and the inhibitory effects were comparable between these mice.
Reference: Eur J Pharmacol. 2013 Nov 15;720(1-3):174-9. https://pubmed.ncbi.nlm.nih.gov/24436989/
Preparing Stock Solutions
The following data is based on the
product
molecular weight
375.89
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. Proudman RGW, Akinaga J, Baker JG. The affinity and selectivity of α-adrenoceptor antagonists, antidepressants and antipsychotics for the human α2A, α2B, and α2C-adrenoceptors and comparison with human α1 and β-adrenoceptors. Pharmacol Res Perspect. 2022 Apr;10(2):e00936. doi: 10.1002/prp2.936. PMID: 35224877; PMCID: PMC8882856.
2. Schwartz DD, Clark TP. Affinity of detomidine, medetomidine and xylazine for alpha-2 adrenergic receptor subtypes. J Vet Pharmacol Ther. 1998 Apr;21(2):107-11. doi: 10.1046/j.1365-2885.1998.00113.x. PMID: 9597647.
3. Serizawa I, Iwasaki N, Ishida H, Saito SY, Ishikawa T. G-protein coupled estrogen receptor-mediated non-genomic facilitatory effect of estrogen on cooling-induced reduction of skin blood flow in mice. Eur J Pharmacol. 2017 Feb 15;797:26-31. doi: 10.1016/j.ejphar.2017.01.013. Epub 2017 Jan 13. PMID: 28089920.
4. Sahara Y, Saito SY, Ishikawa T. Involvement of nitric oxide production in the impairment of skin blood flow response to local cooling in diabetic db/db mice. Eur J Pharmacol. 2013 Nov 15;720(1-3):174-9. PMID: 24436989.
In vitro protocol:
1. Proudman RGW, Akinaga J, Baker JG. The affinity and selectivity of α-adrenoceptor antagonists, antidepressants and antipsychotics for the human α2A, α2B, and α2C-adrenoceptors and comparison with human α1 and β-adrenoceptors. Pharmacol Res Perspect. 2022 Apr;10(2):e00936. doi: 10.1002/prp2.936. PMID: 35224877; PMCID: PMC8882856.
2. Schwartz DD, Clark TP. Affinity of detomidine, medetomidine and xylazine for alpha-2 adrenergic receptor subtypes. J Vet Pharmacol Ther. 1998 Apr;21(2):107-11. doi: 10.1046/j.1365-2885.1998.00113.x. PMID: 9597647.
In vivo protocol:
1. Serizawa I, Iwasaki N, Ishida H, Saito SY, Ishikawa T. G-protein coupled estrogen receptor-mediated non-genomic facilitatory effect of estrogen on cooling-induced reduction of skin blood flow in mice. Eur J Pharmacol. 2017 Feb 15;797:26-31. doi: 10.1016/j.ejphar.2017.01.013. Epub 2017 Jan 13. PMID: 28089920.
2. Sahara Y, Saito SY, Ishikawa T. Involvement of nitric oxide production in the impairment of skin blood flow response to local cooling in diabetic db/db mice. Eur J Pharmacol. 2013 Nov 15;720(1-3):174-9. PMID: 24436989.
1: Qin X, Frech P. Liquid chromatography/mass spectrometry (LC/MS) identification of photooxidative degradates of crystalline and amorphous MK-912. J Pharm Sci. 2001 Jul;90(7):833-44. PubMed PMID: 11458333.
2: Shiue C, Pleus RC, Shiue GG, Rysavy JA, Sunderland JJ, Cornish KG, Young SD, Bylund DB. Synthesis and biological evaluation of [11C]MK-912 as an alpha2-adrenergic receptor radioligand for PET studies. Nucl Med Biol. 1998 Feb;25(2):127-33. PubMed PMID: 9468027.
3: Uhlén S, Xia Y, Chhajlani V, Felder CC, Wikberg JE. [3H]-MK 912 binding delineates two alpha 2-adrenoceptor subtypes in rat CNS one of which is identical with the cloned pA2d alpha 2-adrenoceptor. Br J Pharmacol. 1992 Aug;106(4):986-95. Erratum in: Br J Pharmacol 1993 Mar;108(3):852. PubMed PMID: 1356570; PubMed Central PMCID: PMC1907663.
4: Ortiz-Alonso FJ, Herman WH, Gertz BJ, Williams VC, Smith MJ, Halter JB. Effect of an oral alpha 2-adrenergic blocker (MK-912) on pancreatic islet function in non-insulin-dependent diabetes mellitus. Metabolism. 1991 Nov;40(11):1160-7. PubMed PMID: 1682787.
5: Warren JB, Dollery CT, Fuller RW, Williams VC, Gertz BJ. Assessment of MK-912, an alpha 2-adrenoceptor antagonist, with use of intravenous clonidine. Clin Pharmacol Ther. 1989 Jul;46(1):103-9. PubMed PMID: 2568210.
6: Pettibone DJ, Flagg SD, Totaro JA, Clineschmidt BV, Huff JR, Young SD, Chen R. [3H]L-657,743 (MK-912): a new, high affinity, selective radioligand for brain alpha 2-adrenoceptors. Life Sci. 1989;44(7):459-67. PubMed PMID: 2564617.
