WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 571354
CAS#: 111841-85-1
Description: Abecarnil is a beta carboline and a partial benzodiazepine-receptor agonist that has demonstrated promise as an anxiolytic agent. It may be useful in treating generalized anxiety disorder. In rats, produced a dose-dependent, full reversal of ethanol withdrawal-induced reduction of open arm activity.
MedKoo Cat#: 571354
Name: Abecarnil
CAS#: 111841-85-1
Chemical Formula: C24H24N2O4
Exact Mass: 404.1736
Molecular Weight: 404.47
Elemental Analysis: C, 71.27; H, 5.98; N, 6.93; O, 15.82
Synonym: Abecarnil; ZK 112119; ZK-112119; ZK112119;
IUPAC/Chemical Name: 6-(Benzyloxy)-4-(methoxymethyl)-9H-pyrido[3,4-b]indole-3-carboxylic acid 1-methylethyl ester
InChi Key: RLFKILXOLJVUNF-UHFFFAOYSA-N
InChi Code: InChI=1S/C24H24N2O4/c1-15(2)30-24(27)23-19(14-28-3)22-18-11-17(29-13-16-7-5-4-6-8-16)9-10-20(18)26-21(22)12-25-23/h4-12,15,26H,13-14H2,1-3H3
SMILES Code: O=C(C1=C(COC)C2=C(C=N1)NC3=C2C=C(OCC4=CC=CC=C4)C=C3)OC(C)C
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
| Biological target: | Abecarnil (ZK 112119) is a ligand or a partial agonist for benzodiazepine (BZ) receptor. Abecarnil can act as a positive allosteric modulator of GABAA receptor. Abecarnil inhibits the binding of the BZ [3H]lormetazepam to rat cerebral cortex membranes, with an IC50 of 0.82 nM. |
| In vitro activity: | In vitro, abecarnil inhibited the binding of the BZ [3H]lormetazepam to rat cerebral cortex membranes with an IC50 value of 0.82 nM in comparison to 56 nM for DZP. Reference: J Pharmacol Exp Ther. 1990 Apr;253(1):334-43. https://pubmed.ncbi.nlm.nih.gov/1970361/ |
| In vivo activity: | Abecarnil, a selective benzodiazepine receptor agonist with marked anticonvulsant activity, was administered together with chronic PTZ to evaluate whether persistent activation of GABAA receptors and suppression of seizures during kindling might affect the sensitivity of septohippocampal cholinergic neurons to a challenge dose of PTZ. Abecarnil (1 mg/kg, i.p.) administered 40 min before each PTZ injection neither antagonized the decrease in basal acetylcholine release (2.26 +/- 0.19 pmol per 20-min sample) nor prevented the development of kindling. In contrast, abecarnil prevented the chronic PTZ-induced increase in the sensitivity of acetylcholine release to a challenge dose of PTZ. Reference: J Neurochem. 1997 Jan;68(1):313-8. https://pubmed.ncbi.nlm.nih.gov/8978740/ |
The following data is based on the product molecular weight 404.47 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. Stephens DN, Schneider HH, Kehr W, Andrews JS, Rettig KJ, Turski L, Schmiechen R, Turner JD, Jensen LH, Petersen EN, et al. Abecarnil, a metabolically stable, anxioselective beta-carboline acting at benzodiazepine receptors. J Pharmacol Exp Ther. 1990 Apr;253(1):334-43. PMID: 1970361. 2. Serra M, Dazzi L, Cagetti E, Chessa MF, Pisu MG, Sanna A, Biggio G. Effect of pentylenetetrazole-induced kindling on acetylcholine release in the hippocampus of freely moving rats. J Neurochem. 1997 Jan;68(1):313-8. doi: 10.1046/j.1471-4159.1997.68010313.x. PMID: 8978740. 3. Barbaccia ML, Roscetti G, Bolacchi F, Concas A, Mostallino MC, Purdy RH, Biggio G. Stress-induced increase in brain neuroactive steroids: antagonism by abecarnil. Pharmacol Biochem Behav. 1996 May;54(1):205-10. doi: 10.1016/0091-3057(95)02133-7. PMID: 8728559. |
| In vitro protocol: | 1. Stephens DN, Schneider HH, Kehr W, Andrews JS, Rettig KJ, Turski L, Schmiechen R, Turner JD, Jensen LH, Petersen EN, et al. Abecarnil, a metabolically stable, anxioselective beta-carboline acting at benzodiazepine receptors. J Pharmacol Exp Ther. 1990 Apr;253(1):334-43. PMID: 1970361. |
| In vivo protocol: | 1. Serra M, Dazzi L, Cagetti E, Chessa MF, Pisu MG, Sanna A, Biggio G. Effect of pentylenetetrazole-induced kindling on acetylcholine release in the hippocampus of freely moving rats. J Neurochem. 1997 Jan;68(1):313-8. doi: 10.1046/j.1471-4159.1997.68010313.x. PMID: 8978740. 2. Barbaccia ML, Roscetti G, Bolacchi F, Concas A, Mostallino MC, Purdy RH, Biggio G. Stress-induced increase in brain neuroactive steroids: antagonism by abecarnil. Pharmacol Biochem Behav. 1996 May;54(1):205-10. doi: 10.1016/0091-3057(95)02133-7. PMID: 8728559. |
1: Gale CK, Millichamp J. Generalised anxiety disorder. BMJ Clin Evid. 2011 Oct 27;2011:1002. PMID: 22030083; PMCID: PMC3275153.
2: Pribilla I, Neuhaus R, Huba R, Hillmann M, Turner JD, Stephens DN, Schneider HH. Abecarnil is a full agonist at some, and a partial agonist at other recombinant GABAA receptor subtypes. Psychopharmacol Ser. 1993;11:50-61. doi: 10.1007/978-3-642-78451-4_5. PMID: 7908433.
3: Stephens DN, Turski L, Jones GH, Steppuhn KG, Schneider HH. Abecarnil: a novel anxiolytic with mixed full agonist/partial agonist properties in animal models of anxiety and sedation. Psychopharmacol Ser. 1993;11:79-95. doi: 10.1007/978-3-642-78451-4_7. PMID: 7908435.
4: Mumford GK, Rush CR, Griffiths RR. Abecarnil and alprazolam in humans: behavioral, subjective and reinforcing effects. J Pharmacol Exp Ther. 1995 Feb;272(2):570-80. PMID: 7853170.
5: Stephens DN, Schneider HH, Kehr W, Andrews JS, Rettig KJ, Turski L, Schmiechen R, Turner JD, Jensen LH, Petersen EN, et al. Abecarnil, a metabolically stable, anxioselective beta-carboline acting at benzodiazepine receptors. J Pharmacol Exp Ther. 1990 Apr;253(1):334-43. PMID: 1970361.
6: Duka T, Krause W, Dorow R, Rohloff A, Ott H, Voet B. Abecarnil: a new beta- carboline anxiolytic preliminary clinical pharmacology. Psychopharmacol Ser. 1993;11:132-47. doi: 10.1007/978-3-642-78451-4_11. PMID: 7908432.
7: Jung ME, Wallis CJ, Gatch MB, Lal H. Abecarnil and alprazolam reverse anxiety-like behaviors induced by ethanol withdrawal. Alcohol. 2000 Jun;21(2):161-8. doi: 10.1016/s0741-8329(00)00079-3. PMID: 10963939.
8: Löscher W. Abecarnil shows reduced tolerance development and dependence potential in comparison to diazepam: animal studies. Psychopharmacol Ser. 1993;11:96-112. doi: 10.1007/978-3-642-78451-4_8. PMID: 7908436.
9: Vorobjev VS, Sharonova IN, Skrebitsky VG, Schneider HH, Stephens DN. Abecarnil enhances GABA-induced currents in acutely isolated cerebellar Purkinje cells. Neuropharmacology. 1995 Feb;34(2):157-63. doi: 10.1016/0028-3908(94)00139-j. PMID: 7617141.
10: Small GW, Bystritsky A. Double-blind, placebo-controlled trial of two doses of abecarnil for geriatric anxiety. J Clin Psychiatry. 1997;58 Suppl 11:24-9. PMID: 9363045.
11: Stephens DN, Turski L, Hillman M, Turner JD, Schneider HH, Yamaguchi M. What are the differences between abecarnil and conventional benzodiazepine anxiolytics? Adv Biochem Psychopharmacol. 1992;47:395-405. PMID: 1354919.
12: Serra M, Ghiani CA, Motzo C, Porceddu ML, Biggio G. Antagonism of isoniazid- induced convulsions by abecarnil in mice tolerant to diazepam. Pharmacol Biochem Behav. 1995 Oct;52(2):249-54. doi: 10.1016/0091-3057(94)00422-f. PMID: 8577786.
13: Turski L, Stephens DN, Jensen LH, Petersen EN, Meldrum BS, Patel S, Hansen JB, Löscher W, Schneider HH, Schmiechen R. Anticonvulsant action of the beta- carboline abecarnil: studies in rodents and baboon, Papio papio. J Pharmacol Exp Ther. 1990 Apr;253(1):344-52. PMID: 1970362.
14: Natolino F, Zanotti A, Contarino A, Lipartiti M, Giusti P. Abecarnil, a beta-carboline derivative, does not exhibit anticonvulsant tolerance or withdrawal effects in mice. Naunyn Schmiedebergs Arch Pharmacol. 1996 Nov;354(5):612-7. doi: 10.1007/BF00170836. PMID: 8938660.
15: Krause W, Duka T, Matthes H. Pharmacokinetics and biotransformation of the anxiolytic abecarnil in healthy volunteers. Xenobiotica. 1991 Jun;21(6):763-74. doi: 10.3109/00498259109039516. PMID: 1683073.
16: Steppuhn KG, Schneider HH, Turski L, Stephens DN. Long-term treatment with abecarnil does not induce diazepam-like dependence in mice. J Pharmacol Exp Ther. 1993 Mar;264(3):1395-400. PMID: 8095551.
17: Ozawa M, Nakada Y, Sugimachi K, Yabuuchi F, Akai T, Mizuta E, Kuno S, Yamaguchi M. Pharmacological characterization of the novel anxiolytic beta- carboline abecarnil in rodents and primates. Jpn J Pharmacol. 1994 Mar;64(3):179-87. doi: 10.1254/jjp.64.179. PMID: 7912751.
18: Cooper SJ, Greenwood SE. The beta-carboline abecarnil, a novel agonist at central benzodiazepine receptors, influences saccharin and salt taste preferences in the rat. Brain Res. 1992 Dec 18;599(1):144-7. doi: 10.1016/0006-8993(92)90862-4. PMID: 1337300.
19: Ozawa M, Sugimachi K, Nakada-Kometani Y, Akai T, Yamaguchi M. Chronic pharmacological activities of the novel anxiolytic beta-carboline abecarnil in rats. J Pharmacol Exp Ther. 1994 May;269(2):457-62. PMID: 7910208.
20: Hege SG, Ellinwood EH Jr, Wilson WH, Helligers CA, Graham SM. Psychomotor effects of the anxiolytic abecarnil: a comparison with lorazepam. Psychopharmacology (Berl). 1997 May;131(2):101-7. doi: 10.1007/s002130050271. PMID: 9201796.
