WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H326913
CAS#: 84379-13-5
Description: Bretazenil, also known as Ro 16-6028, is GABA A receptor agonist potentially for the treatment of anxiety disorders. Bretazenil differs from traditional 1,4-benzodiazepines by being a partial agonist and because it binds to α1, α2, α3, α4, α5 and α6 subunit containing GABAA receptor benzodiazepine receptor complexes. 1,4-benzodiazepines bind only to α1, α2, α3 and α5 GABAA benzodiazepine receptor complexes.
Hodoodo Cat#: H326913
Name: Bretazenil
CAS#: 84379-13-5
Chemical Formula: C19H20BrN3O3
Exact Mass: 417.07
Molecular Weight: 418.291
Elemental Analysis: C, 54.56; H, 4.82; Br, 19.10; N, 10.05; O, 11.47
Synonym: Ro 16-6028; Ro 16 6028; Ro16-6028; Ro 166028; Ro 166028; Ro166028; Ro 16-6028/000; Bretazenil
IUPAC/Chemical Name: tert-butyl (S)-8-bromo-9-oxo-11,12,13,13a-tetrahydro-9H-benzo[e]imidazo[5,1-c]pyrrolo[1,2-a][1,4]diazepine-1-carboxylate
InChi Key: LWUDDYHYYNNIQI-ZDUSSCGKSA-N
InChi Code: InChI=1S/C19H20BrN3O3/c1-19(2,3)26-18(25)15-16-13-8-5-9-22(13)17(24)14-11(20)6-4-7-12(14)23(16)10-21-15/h4,6-7,10,13H,5,8-9H2,1-3H3/t13-/m0/s1
SMILES Code: O=C(C1=C([C@@]2([H])N3CCC2)N(C=N1)C4=CC=CC(Br)=C4C3=O)OC(C)(C)C
Appearance: Solid powder
Purity: >97% (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:
| Biological target: | Bretazenil is a partial agonist at the GABAA benzodiazepine site (EC50 = 10 nM at α1β1γ2 receptors). |
| In vitro activity: | The differences in intrinsic activity and receptor subtype specificity of the newly developed benzodiazepine receptor ligands bretazenil, divaplon and abecarnil were assessed in recombinant gamma-aminobutyric acidA (GABAA) receptors expressed in mammalian cells. Bretazenil displayed an intrinsic activity which amounted only to 58 +/- 7% and 35 +/- 11% of that of flunitrazepam at the alpha 3 beta 2 gamma 2 and alpha 5 beta 2 gamma 2 combination, respectively. Thus, the partial agonism postulated for bretazenil and divaplon on pharmacological grounds is shown to be operative on the level of single GABAA receptors. Reference: J Pharmacol Exp Ther. 1993 Jul;266(1):385-91. https://pubmed.ncbi.nlm.nih.gov/8392559/ |
| In vivo activity: | Alzet minipumps were loaded with bretazenil, a GABAA receptor partial agonist, and implanted subcutaneously to deliver 750 ng/hr for 14 days. After 3 baseline days with the bretazenil-eluting minipump, the AgrpDTR/+ mice were treated with DT (diptheria toxin). Food consumption by the bretazenil-treated group fell for the first 6 days after DT treatment, but then also returned to normal over the next 12 days. Bretazenil (0.2 mg/kg, ip) increased food consumption by wild-type mice during the first 4 hr, but 24-hr food intake was normal. Chronic delivery of bretazenil to wild-type animals for 10 days via a minipump had no effect on body weight. Once-daily administration of bretazenil (0.2 mg/kg, ip) was ineffective at preventing starvation after AgRP neuron ablation, suggesting that chronic activation of GABAA receptors is an important aspect of the rescue strategy. Chronic treatment with bretazenil also restored intra-oral sucrose consumption to >80% of original after ablation of AgRP neurons. Thus, both consummatory and appetitive responses are rescued by bretazenil treatment after AgRP neuron ablation. Reference: Cell. 2009 Jun 26;137(7):1225-34. https://pubmed.ncbi.nlm.nih.gov/19563755/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 35.9 | 86.11 | |
| Ethanol | 30.9 | 73.92 |
The following data is based on the product molecular weight 418.29 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. Puia G, Ducic I, Vicini S, Costa E. Molecular mechanisms of the partial allosteric modulatory effects of bretazenil at gamma-aminobutyric acid type A receptor. Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3620-4. doi: 10.1073/pnas.89.8.3620. PMID: 1373505; PMCID: PMC48920. 2. Knoflach F, Drescher U, Scheurer L, Malherbe P, Mohler H. Full and partial agonism displayed by benzodiazepine receptor ligands at recombinant gamma-aminobutyric acidA receptor subtypes. J Pharmacol Exp Ther. 1993 Jul;266(1):385-91. PMID: 8392559. 3. . Kimoto S, Muraki K, Toritsuka M, Mugikura S, Kajiwara K, Kishimoto T, Illingworth E, Tanigaki K. Selective overexpression of Comt in prefrontal cortex rescues schizophrenia-like phenotypes in a mouse model of 22q11 deletion syndrome. Transl Psychiatry. 2012 Aug 7;2(8):e146. doi: 10.1038/tp.2012.70. PMID: 22872161; PMCID: PMC3432186. 4. Wu Q, Boyle MP, Palmiter RD. Loss of GABAergic signaling by AgRP neurons to the parabrachial nucleus leads to starvation. Cell. 2009 Jun 26;137(7):1225-34. doi: 10.1016/j.cell.2009.04.022. PMID: 19563755; PMCID: PMC2729323. |
| In vitro protocol: | 1. Puia G, Ducic I, Vicini S, Costa E. Molecular mechanisms of the partial allosteric modulatory effects of bretazenil at gamma-aminobutyric acid type A receptor. Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3620-4. doi: 10.1073/pnas.89.8.3620. PMID: 1373505; PMCID: PMC48920. 2. Knoflach F, Drescher U, Scheurer L, Malherbe P, Mohler H. Full and partial agonism displayed by benzodiazepine receptor ligands at recombinant gamma-aminobutyric acidA receptor subtypes. J Pharmacol Exp Ther. 1993 Jul;266(1):385-91. PMID: 8392559. |
| In vivo protocol: | 1. . Kimoto S, Muraki K, Toritsuka M, Mugikura S, Kajiwara K, Kishimoto T, Illingworth E, Tanigaki K. Selective overexpression of Comt in prefrontal cortex rescues schizophrenia-like phenotypes in a mouse model of 22q11 deletion syndrome. Transl Psychiatry. 2012 Aug 7;2(8):e146. doi: 10.1038/tp.2012.70. PMID: 22872161; PMCID: PMC3432186. 2. Wu Q, Boyle MP, Palmiter RD. Loss of GABAergic signaling by AgRP neurons to the parabrachial nucleus leads to starvation. Cell. 2009 Jun 26;137(7):1225-34. doi: 10.1016/j.cell.2009.04.022. PMID: 19563755; PMCID: PMC2729323. |
1: Licata SC, Rowlett JK. Self-administration of bretazenil under progressive-ratio schedules: behavioral economic analysis of the role intrinsic efficacy plays in the reinforcing effects of benzodiazepines. Drug Alcohol Depend. 2011 Jan 15;113(2-3):157-64. doi: 10.1016/j.drugalcdep.2010.07.019. Epub 2010 Aug 30. PubMed PMID: 20800977; PubMed Central PMCID: PMC3025040.
2: Munro G, Lopez-Garcia JA, Rivera-Arconada I, Erichsen HK, Nielsen EØ, Larsen JS, Ahring PK, Mirza NR. Comparison of the novel subtype-selective GABAA receptor-positive allosteric modulator NS11394 [3'-[5-(1-hydroxy-1-methyl-ethyl)-benzoimidazol-1-yl]-biphenyl-2-carbonitrile] with diazepam, zolpidem, bretazenil, and gaboxadol in rat models of inflammatory and neuropathic pain. J Pharmacol Exp Ther. 2008 Dec;327(3):969-81. doi: 10.1124/jpet.108.144568. Epub 2008 Sep 12. PubMed PMID: 18791060.
3: Mares P, Slamberová R. Efficacy of bretazenil against cortical epileptic afterdischarges increases during early ontogeny in rats. Pharmacol Rep. 2006 Jul-Aug;58(4):519-25. PubMed PMID: 16963798.
4: Mirza NR, Rodgers RJ, Mathiasen LS. Comparative cue generalization profiles of L-838, 417, SL651498, zolpidem, CL218,872, ocinaplon, bretazenil, zopiclone, and various benzodiazepines in chlordiazepoxide and zolpidem drug discrimination. J Pharmacol Exp Ther. 2006 Mar;316(3):1291-9. Epub 2005 Dec 8. PubMed PMID: 16339395.
5: Mathiasen L, Mirza NR. A comparison of chlordiazepoxide, bretazenil, L838,417 and zolpidem in a validated mouse Vogel conflict test. Psychopharmacology (Berl). 2005 Nov;182(4):475-84. Epub 2005 Oct 19. PubMed PMID: 16133136.
6: Weerts EM, Ator NA, Kaminski BJ, Griffiths RR. Comparison of the behavioral effects of bretazenil and flumazenil in triazolam-dependent and non-dependent baboons. Eur J Pharmacol. 2005 Sep 5;519(1-2):103-13. PubMed PMID: 16129429.
7: Tuk B, van Gool T, Danhof M. Mechanism-based pharmacodynamic modeling of the interaction of midazolam, bretazenil, and zolpidem with ethanol. J Pharmacokinet Pharmacodyn. 2002 Jun;29(3):235-50. PubMed PMID: 12449497.
8: Tashma Z, Raveh L, Liani H, Alkalay D, Givoni S, Kapon J, Cohen G, Alcalay M, Grauer E. Bretazenil, a benzodiazepine receptor partial agonist, as an adjunct in the prophylactic treatment of OP poisoning. J Appl Toxicol. 2001 Dec;21 Suppl 1:S115-9. PubMed PMID: 11920931.
9: López-Romero B, Evrard G, Durant F, Sevrin M, George P. Molecular structure and stereoelectronic properties of sarmazenil--a weak inverse agonist at the omega modulatory sites (benzodiazepine receptors): comparison with bretazenil and flumazenil. Bioorg Med Chem. 1998 Oct;6(10):1745-57. PubMed PMID: 9839004.
10: Witkin JM, Acri JB, Gleeson S, Barrett JE. Blockade of behavioral effects of bretazenil by flumazenil and ZK 93,426 in pigeons. Pharmacol Biochem Behav. 1997 Jan;56(1):1-7. PubMed PMID: 8981602.
11: Clifton PG, Cooper SJ. The benzodiazepine partial receptor agonist, bretazenil, provokes a strong hyperphagic response: a meal pattern analysis in free feeding rats. Behav Pharmacol. 1996 Oct;7(5):454-461. PubMed PMID: 11224441.
12: Delini-Stula A, Berdah-Tordjman D. Antipsychotic effects of bretazenil, a partial benzodiazepine agonist in acute schizophrenia--a study group report. J Psychiatr Res. 1996 Jul-Aug;30(4):239-50. PubMed PMID: 8905533.
13: Bronson M, Chen HC. Time course of discriminative stimulus effects of bretazenil and chlordiazepoxide in rats. Eur J Pharmacol. 1996 Jun 3;305(1-3):7-12. PubMed PMID: 8813525.
14: van Steveninck AL, Gieschke R, Schoemaker RC, Roncari G, Tuk B, Pieters MS, Breimer DD, Cohen AF. Pharmacokinetic and pharmacodynamic interactions of bretazenil and diazepam with alcohol. Br J Clin Pharmacol. 1996 Jun;41(6):565-73. PubMed PMID: 8799523; PubMed Central PMCID: PMC2042631.
15: Acri JB, Serdikoff SL, Witkin JM, Sannerud CA. Discriminative stimulus effects of the benzodiazepine receptor partial agonist bretazenil in pigeons and in rats. Behav Pharmacol. 1996 Jan;7(1):72-77. PubMed PMID: 11224396.
16: Guldner J, Trachsel L, Kratschmayr C, Rothe B, Holsboer F, Steiger A. Bretazenil modulates sleep EEG and nocturnal hormone secretion in normal men. Psychopharmacology (Berl). 1995 Nov;122(2):115-21. PubMed PMID: 8848526.
17: Rundfeldt C, Wlaź P, Hönack D, Löscher W. Anticonvulsant tolerance and withdrawal characteristics of benzodiazepine receptor ligands in different seizure models in mice. Comparison of diazepam, bretazenil and abecarnil. J Pharmacol Exp Ther. 1995 Nov;275(2):693-702. PubMed PMID: 7473156.
18: Bronson ME. Chronic bretazenil produces tolerance to chlordiazepoxide, midazolam, and abecarnil. Pharmacol Biochem Behav. 1995 Jun-Jul;51(2-3):481-90. PubMed PMID: 7667373.
19: Mehta AK, Shank RP. Interaction of abecarnil, bretazenil, and RO 19-8022 with diazepam-sensitive and -insensitive benzodiazepine sites in the rat cerebellum and cerebral cortex. Life Sci. 1995;57(24):2215-22. PubMed PMID: 7475974.
20: Gieschke R, Cluydts R, Dingemanse J, De Roeck J, De Cock W. Effects of bretazenil vs. zolpidem and placebo on experimentally induced sleep disturbance in healthy volunteers. Methods Find Exp Clin Pharmacol. 1994 Nov;16(9):667-75. PubMed PMID: 7746029.
