Synonym
AWD 131-138; AWD-131-138; AWD131-138; AWD 131138; Imepitoin.
IUPAC/Chemical Name
1-(4-Chlorophenyl)-1,5-dihydro-4-(4-morpholinyl)-2H-imidazol-2-one
InChi Key
IQHYCZKIFIHTAI-UHFFFAOYSA-N
InChi Code
InChI=1S/C13H14ClN3O2/c14-10-1-3-11(4-2-10)17-9-12(15-13(17)18)16-5-7-19-8-6-16/h1-4H,5-9H2
SMILES Code
O=C1N=C(N2CCOCC2)CN1C3=CC=C(Cl)C=C3
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:
Imepitoin (AWD 131-138) is a new low-affinity partial benzodiazepine receptor agonist with potent anticonvulsant and anxiolytic properties in rodent models.
In vitro activity:
The in vitro study indicated that imepitoin (at doses of 1 and 10 μM) acts to decrease neuronal activity induced by CRF but not the basal (spontaneous pacemaker) activity in mouse LC neurons. The half-maximal inhibition could be determined to 60 nM for diazepam and 520 nM for imepitoin, respectively (Figure 1).
Reference: Front Pharmacol. 2018 Nov 1;9:1225. https://pubmed.ncbi.nlm.nih.gov/30455643/
In vivo activity:
In the 16-item owner report of fear and anxiety signs, fear and anxiety behaviors were significantly reduced under imepitoin treatment compared to placebo (delta -6.1 scoring points; P < .0001). A significantly higher proportion of owners reported a good or excellent overall treatment effect in the imepitoin group compared to placebo (odds ratio 4.689; 95% CI, 2.79-7.89; P < .0001). Imepitoin effectively controls fear and anxiety associated with noise phobia in dogs.
Reference: J Vet Intern Med. 2019 Nov;33(6):2675-2684. https://pubmed.ncbi.nlm.nih.gov/31568622/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMF |
10.0 |
35.75 |
| DMSO |
17.5 |
62.56 |
| DMSO:PBS (pH 7.2) (1:1) |
0.5 |
1.79 |
| Ethanol |
1.1 |
4.02 |
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
279.72
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. Engel O, Masic A, Landsberg G, Brooks M, Mills DS, Rundfeldt C. Imepitoin Shows Benzodiazepine-Like Effects in Models of Anxiety. Front Pharmacol. 2018 Nov 1;9:1225. doi: 10.3389/fphar.2018.01225. PMID: 30455643; PMCID: PMC6230983.
2. Engel O, Müller HW, Klee R, Francke B, Mills DS. Effectiveness of imepitoin for the control of anxiety and fear associated with noise phobia in dogs. J Vet Intern Med. 2019 Nov;33(6):2675-2684. doi: 10.1111/jvim.15608. Epub 2019 Sep 30. PMID: 31568622; PMCID: PMC6872611.
3. Sigel E, Baur R, Netzer R, Rundfeldt C. The antiepileptic drug AWD 131-138 stimulates different recombinant isoforms of the rat GABA(A) receptor through the benzodiazepine binding site. Neurosci Lett. 1998 Apr 3;245(2):85-8. doi: 10.1016/s0304-3940(98)00186-4. PMID: 9605491.
In vitro protocol:
1. Engel O, Masic A, Landsberg G, Brooks M, Mills DS, Rundfeldt C. Imepitoin Shows Benzodiazepine-Like Effects in Models of Anxiety. Front Pharmacol. 2018 Nov 1;9:1225. doi: 10.3389/fphar.2018.01225. PMID: 30455643; PMCID: PMC6230983.
In vivo protocol:
1. Engel O, Müller HW, Klee R, Francke B, Mills DS. Effectiveness of imepitoin for the control of anxiety and fear associated with noise phobia in dogs. J Vet Intern Med. 2019 Nov;33(6):2675-2684. doi: 10.1111/jvim.15608. Epub 2019 Sep 30. PMID: 31568622; PMCID: PMC6872611.
2. Sigel E, Baur R, Netzer R, Rundfeldt C. The antiepileptic drug AWD 131-138 stimulates different recombinant isoforms of the rat GABA(A) receptor through the benzodiazepine binding site. Neurosci Lett. 1998 Apr 3;245(2):85-8. doi: 10.1016/s0304-3940(98)00186-4. PMID: 9605491.
1: Royaux E, Bhatti S, De Cock H, Van Ham L, Kitshoff A, Vandenabeele S. Cutaneous adverse drug reaction in a dog associated with imepitoin. Vet Dermatol. 2016 Apr;27(2):118-e32. doi: 10.1111/vde.12289. Epub 2016 Jan 22. PubMed PMID: 26799469.
2: Rundfeldt C, Tipold A, Löscher W. Efficacy, safety, and tolerability of imepitoin in dogs with newly diagnosed epilepsy in a randomized controlled clinical study with long-term follow up. BMC Vet Res. 2015 Sep 2;11:228. doi: 10.1186/s12917-015-0548-9. PubMed PMID: 26330063; PubMed Central PMCID: PMC4556053.
3: Packer RM, Volk HA. Study on the effects of imepitoin on the behaviour of dogs with epilepsy. Vet Rec. 2015 Aug 1;177(5):132. doi: 10.1136/vr.h4108. PubMed PMID: 26231879.
4: Tipold A, Keefe TJ, Löscher W, Rundfeldt C, de Vries F. Clinical efficacy and safety of imepitoin in comparison with phenobarbital for the control of idiopathic epilepsy in dogs. J Vet Pharmacol Ther. 2015 Apr;38(2):160-8. doi: 10.1111/jvp.12151. Epub 2014 Jul 31. PubMed PMID: 25079881.
5: Rundfeldt C, Gasparic A, Wlaź P. Imepitoin as novel treatment option for canine idiopathic epilepsy: pharmacokinetics, distribution, and metabolism in dogs. J Vet Pharmacol Ther. 2014 Oct;37(5):421-34. doi: 10.1111/jvp.12117. Epub 2014 Mar 10. PubMed PMID: 24611573; PubMed Central PMCID: PMC4280904.
6: Rundfeldt C, Löscher W. The pharmacology of imepitoin: the first partial benzodiazepine receptor agonist developed for the treatment of epilepsy. CNS Drugs. 2014 Jan;28(1):29-43. doi: 10.1007/s40263-013-0129-z. Review. PubMed PMID: 24357084.
7: Löscher W, Hoffmann K, Twele F, Potschka H, Töllner K. The novel antiepileptic drug imepitoin compares favourably to other GABA-mimetic drugs in a seizure threshold model in mice and dogs. Pharmacol Res. 2013 Nov;77:39-46. doi: 10.1016/j.phrs.2013.09.003. Epub 2013 Sep 18. PubMed PMID: 24056205.
