AZD-2327

AZD-2327
Clinical data
Other namesAZD 2327; AZD2327
Routes of
administration		Oral[1][2]
Drug classδ-Opioid receptor agonist[1]
Identifiers
  • 4-[(R)-(3-aminophenyl)-[4-[(4-fluorophenyl)methyl]piperazin-1-yl]methyl]-N,N-diethylbenzamide
CAS Number
PubChem CID
ChemSpider
UNII
Chemical and physical data
FormulaC29H35FN4O
Molar mass474.624 g·mol−1
3D model (JSmol)
  • CCN(CC)C(=O)C1=CC=C(C=C1)[C@H](C2=CC(=CC=C2)N)N3CCN(CC3)CC4=CC=C(C=C4)F
  • InChI=1S/C29H35FN4O/c1-3-33(4-2)29(35)24-12-10-23(11-13-24)28(25-6-5-7-27(31)20-25)34-18-16-32(17-19-34)21-22-8-14-26(30)15-9-22/h5-15,20,28H,3-4,16-19,21,31H2,1-2H3/t28-/m1/s1
  • Key:XGFLMBBZEPJGHY-MUUNZHRXSA-N

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]

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]

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]

  1. ^ a b c d e f g "AZD 2327". AdisInsight. 5 November 2023. Retrieved 21 October 2024.
  2. ^ a b c "Delving into the Latest Updates on AZD-2327 with Synapse". Synapse. 19 October 2024. Retrieved 21 October 2024.
  3. ^ a b c d e f g Mandrioli R, Mercolini L (April 2015). "Discontinued anxiolytic drugs (2009 - 2014)". Expert Opin Investig Drugs. 24 (4): 557–573. doi:10.1517/13543784.2014.998335. PMID 25557457.
  4. ^ a b c d Dripps IJ, Jutkiewicz EM (2018). "Delta Opioid Receptors and Modulation of Mood and Emotion". Handb Exp Pharmacol. 247: 179–197. doi:10.1007/164_2017_42. PMID 28993835.
  5. ^ Richards, Erica M.; Mathews, Daniel C.; Luckenbaugh, David A.; Ionescu, Dawn F.; Machado-Vieira, Rodrigo; Niciu, Mark J.; Duncan, Wallace C.; Nolan, Neal M.; Franco-Chaves, Jose A.; Hudzik, Thomas; Maciag, Carla; Li, Shuang; Cross, Alan; Smith, Mark A.; Zarate, Carlos A. (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. ISSN 0033-3158. PMC 5103283. PMID 26728893.
  6. ^ Hudzik, T.J.; Pietras, M.R.; Caccese, R.; Bui, K.H.; Yocca, F.; Paronis, C.A.; M.D.B., Swedberg (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.
  7. ^ Guo, Jian; Zhou, Diansong; Li, Yan; Khanh, Bui H. (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. ISSN 0142-2782. PMID 26081137.
  8. ^ a b Hudzik, T. J.; Maciag, C.; Smith, M. A.; Caccese, R.; Pietras, M. R.; Bui, K. H.; Coupal, M.; Adam, L.; Payza, K.; Griffin, A.; Smagin, G.; Song, D.; Swedberg, M. D. B.; Brown, W. (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. ISSN 1521-0103. PMID 21444630.
  9. ^ Rosenberg, Howard C.; Chiu, Ted H. (March 1985). "Time course for development of benzodiazepine tolerance and physical dependence". Neuroscience & Biobehavioral Reviews. 9 (1): 123–131. doi:10.1016/0149-7634(85)90038-7. PMID 2858077.
  10. ^ 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.
  11. ^ Sanches M, Quevedo J, Soares JC (March 2021). "New agents and perspectives in the pharmacological treatment of major depressive disorder". Prog Neuropsychopharmacol Biol Psychiatry. 106: 110157. doi:10.1016/j.pnpbp.2020.110157. PMC 7750246. PMID 33159975.