Chemistry:AZD-2327
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]
Pharmacology
The 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
AZD-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
References
- ↑ 1.0 1.1 1.2 1.3 1.4 "AZD 2327". 5 November 2023. https://adisinsight.springer.com/drugs/800024943.
- ↑ 2.0 2.1 "Delving into the Latest Updates on AZD-2327 with Synapse". 19 October 2024. https://synapse.patsnap.com/drug/bd0f9b65bcbc41b3ad7962bc57bd44ab.
- ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 "Discontinued anxiolytic drugs (2009 - 2014)". Expert Opinion on Investigational Drugs 24 (4): 557–573. April 2015. doi:10.1517/13543784.2014.998335. PMID 25557457.
- ↑ 4.0 4.1 4.2 4.3 "Delta Opioid Receptors and Modulation of Mood and Emotion". Delta Opioid Receptor Pharmacology and Therapeutic Applications. Handbook of Experimental Pharmacology. 247. 2018. pp. 179–197. doi:10.1007/164_2017_42. ISBN 978-3-319-95131-7.
- ↑ "A randomized, placebo-controlled pilot trial of the delta opioid receptor agonist AZD2327 in anxious depression". Psychopharmacology 233 (6): 1119–1130. March 2016. doi:10.1007/s00213-015-4195-4. PMID 26728893.
- ↑ "Effects of the δ opioid agonist AZD2327 upon operant behaviors and assessment of its potential for abuse". Pharmacology, Biochemistry, and Behavior 124: 48–57. September 2014. doi:10.1016/j.pbb.2014.05.009. PMID 24857840.
- ↑ "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. November 2015. doi:10.1002/bdd.1962. PMID 26081137.
- ↑ 8.0 8.1 "Preclinical pharmacology of AZD2327: a highly selective agonist of the δ-opioid receptor". The Journal of Pharmacology and Experimental Therapeutics 338 (1): 195–204. July 2011. doi:10.1124/jpet.111.179432. PMID 21444630.
- ↑ "Time course for development of benzodiazepine tolerance and physical dependence". Neuroscience and Biobehavioral Reviews 9 (1): 123–131. March 1985. doi:10.1016/0149-7634(85)90038-7. PMID 2858077.
- ↑ "Novel Antidepressants in the Pipeline (Phase II and III): A Systematic Review of the US Clinical Trials Registry". Pharmacopsychiatry 55 (4): 193–202. July 2022. doi:10.1055/a-1714-9097. PMID 35045580.
- ↑ "New agents and perspectives in the pharmacological treatment of major depressive disorder". Progress in Neuro-Psychopharmacology & Biological Psychiatry 106. March 2021. doi:10.1016/j.pnpbp.2020.110157. PMID 33159975.
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