AZD-2327 is a δ-opioid receptor agonist which was under development for the treatment of depressive disorders and anxiety disorders but was never marketed.[1][2][3][4][5] It is taken by mouth.[1]
 | |
| Clinical data | |
|---|---|
| Other names | AZD 2327; AZD2327 |
| Routes of administration | Oral[1][2] |
| Drug class | δ-Opioid receptor agonist[1] |
| Identifiers | |
| |
| CAS Number |
|
| PubChem CID | |
| ChemSpider | |
| UNII | |
| ECHA InfoCard | 100.170.827 |
| Chemical and physical data | |
| Formula | C29H35FN4O |
| Molar mass | 474.624 g·mol−1 |
| 3D model (JSmol) | |
| |
| |
Pharmacology
editThe drug showed antidepressant- and anxiolytic-like effects as well as locomotor-stimulating effects in animal models.[3][4] It had reduced induction of seizures and locomotor hyperactivity compared to other δ-opioid receptor agonists.[3][4] The doses required for stimulant-like activity were 3- to 10-fold greater than the doses that produced antidepressant- and anxiolytic-like effects.[4] The drug appears to have a very low misuse potential based on animal studies.[3][6] In addition to its δ-opioid receptor agonist activity, AZD-2327 has been reported to act as a cytochrome P450 CYP3A4 inhibitor.[7]
It has been found to inhibit the release of norepinephrine caused by anxiety and was able to do so as much as the benzodiazepine diazepam.[8] However, AZD-2327 could be advantageous to benzodiazepines because these drugs often cause rapid tolerance and dependence.[9] In contrast to benzodiazepines, AZD-2327 may have less or no potential for tolerance in terms of its anxiolytic-like effects.[8]
History
editAZD-2327 was first described by 2004 and was first described in the scientific literature in 2009.[3] The development of AZD-2327 was discontinued in 2010.[3][1] It reached phase 2 clinical trials for both depressive disorders and anxiety disorders prior to its discontinuation.[1] No reason was given for the discontinuation of its development.[3] However, the drug was found to be ineffective for major depressive disorder in a phase 2 clinical trial.[10][11] AZD-2327 was developed by AstraZeneca.[1][2]
See also
editReferences
edit- ^ a b c d e f g "AZD 2327". AdisInsight. 5 November 2023. Retrieved 21 October 2024.
- ^ a b c "Delving into the Latest Updates on AZD-2327 with Synapse". Synapse. 19 October 2024. Retrieved 21 October 2024.
- ^ a b c d e f g Mandrioli R, Mercolini L (April 2015). "Discontinued anxiolytic drugs (2009 - 2014)". Expert Opinion on Investigational Drugs. 24 (4): 557–573. doi:10.1517/13543784.2014.998335. PMID 25557457.
- ^ a b c d Dripps IJ, Jutkiewicz EM (2018). "Delta Opioid Receptors and Modulation of Mood and Emotion". Handbook of Experimental Pharmacology. Handbook of Experimental Pharmacology. 247: 179–197. doi:10.1007/164_2017_42. ISBN 978-3-319-95131-7. PMID 28993835.
- ^ Richards EM, Mathews DC, Luckenbaugh DA, Ionescu DF, Machado-Vieira R, Niciu MJ, et al. (March 2016). "A randomized, placebo-controlled pilot trial of the delta opioid receptor agonist AZD2327 in anxious depression". Psychopharmacology. 233 (6): 1119–1130. doi:10.1007/s00213-015-4195-4. PMC 5103283. PMID 26728893.
- ^ Hudzik TJ, Pietras MR, Caccese R, Bui KH, Yocca F, Paronis CA, et al. (September 2014). "Effects of the δ opioid agonist AZD2327 upon operant behaviors and assessment of its potential for abuse". Pharmacology, Biochemistry, and Behavior. 124: 48–57. doi:10.1016/j.pbb.2014.05.009. PMID 24857840.
- ^ Guo J, Zhou D, Li Y, Khanh BH (November 2015). "Physiologically based pharmacokinetic modeling to predict complex drug-drug interactions: a case study of AZD2327 and its metabolite, competitive and time-dependent CYP3A inhibitors". Biopharmaceutics & Drug Disposition. 36 (8): 507–519. doi:10.1002/bdd.1962. PMID 26081137.
- ^ a b Hudzik TJ, Maciag C, Smith MA, Caccese R, Pietras MR, Bui KH, et al. (July 2011). "Preclinical pharmacology of AZD2327: a highly selective agonist of the δ-opioid receptor". The Journal of Pharmacology and Experimental Therapeutics. 338 (1): 195–204. doi:10.1124/jpet.111.179432. PMID 21444630.
- ^ Rosenberg HC, Chiu TH (March 1985). "Time course for development of benzodiazepine tolerance and physical dependence". Neuroscience and Biobehavioral Reviews. 9 (1): 123–131. doi:10.1016/0149-7634(85)90038-7. PMID 2858077.
- ^ Sakurai H, Yonezawa K, Tani H, Mimura M, Bauer M, Uchida H (July 2022). "Novel Antidepressants in the Pipeline (Phase II and III): A Systematic Review of the US Clinical Trials Registry". Pharmacopsychiatry. 55 (4): 193–202. doi:10.1055/a-1714-9097. PMC 9259184. PMID 35045580.
- ^ Sanches M, Quevedo J, Soares JC (March 2021). "New agents and perspectives in the pharmacological treatment of major depressive disorder". Progress in Neuro-Psychopharmacology & Biological Psychiatry. 106: 110157. doi:10.1016/j.pnpbp.2020.110157. PMC 7750246. PMID 33159975.