Pharmaceutical compound
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| Other names | AZD 2327; AZD2327 |
| Routes of administration | Oral |
| Drug class | δ-Opioid receptor agonist |
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IUPAC name
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| ECHA InfoCard | 100.170.827  |
| Chemical and physical data | |
| Formula | C29H35FN4O |
| Molar mass | 474.624 g·mol |
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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. It is taken by mouth.
Pharmacology
The drug showed antidepressant- and anxiolytic-like effects as well as locomotor-stimulating effects in animal models. It had reduced induction of seizures and locomotor hyperactivity compared to other δ-opioid receptor agonists. The doses required for stimulant-like activity were 3- to 10-fold greater than the doses that produced antidepressant- and anxiolytic-like effects. The drug appears to have a very low misuse potential based on animal studies. In addition to its δ-opioid receptor agonist activity, AZD-2327 has been reported to act as a cytochrome P450 CYP3A4 inhibitor.
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. However, AZD-2327 could be advantageous to benzodiazepines because these drugs often cause rapid tolerance and dependence. In contrast to benzodiazepines, AZD-2327 may have less or no potential for tolerance in terms of its anxiolytic-like effects.
History
AZD-2327 was first described by 2004 and was first described in the scientific literature in 2009. The development of AZD-2327 was discontinued in 2010. It reached phase 2 clinical trials for both depressive disorders and anxiety disorders prior to its discontinuation. No reason was given for the discontinuation of its development. However, the drug was found to be ineffective for major depressive disorder in a phase 2 clinical trial. AZD-2327 was developed by AstraZeneca.
See also
References
- ^ "AZD 2327". AdisInsight. 5 November 2023. Retrieved 21 October 2024.
- ^ "Delving into the Latest Updates on AZD-2327 with Synapse". Synapse. 19 October 2024. Retrieved 21 October 2024.
- ^ 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.
- ^ 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.
- ^ 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.