Benzimidazole opioids
Benzimidazole opioids are a class of synthetic opioids that contain a benzimidazole core structure. The pain-relieving properties of these substances were discovered in the mid-1950s by the Swiss company Ciba AG. The most important subgroup are the nitazene opioids, which since 2019 have become increasingly widespread as narcotics in North America and Europe, as well as West Africa. Some other benzimidazole-containing opioids are classified separately under the orphine subgroup. There is currently no medical usage due to the high potencies of certain analogs.[1]
History
[edit]
In 1957, the pharmaceutical research department of Ciba AG published the discovery of the (low) analgesic effect of 1-(β-diethylaminoethyl)-2-benzylbenzimidazole (desnitazene).[2] Shortly afterwards, the nitazenes were discovered in structure-activity relationship studies.[3][4]
Mechanism of action
[edit]Benzimidazole opioids are μ-opioid receptor agonists, similar to other synthetic opioids, and may exhibit significantly higher potencies than that of morphine.[5][6] However, the potency of a given benzimidazole opioid can vary greatly depending on its structure: isotonitazene is estimated to be hundreds of times more potent than fentanyl while butonitazene is estimated to be less potent than morphine.[7] Furthermore, some benzimidazole opioids have also been developed to target other pathways, such as the inhibition of nitric oxide synthase.[8]
See also
[edit]References
[edit]- ↑ Montanari E, Madeo G, Pichini S, Busardò FP, Carlier J (August 2022). "Acute Intoxications and Fatalities Associated with Benzimidazole Opioid (Nitazene Analog) Use: A Systematic Review". Therapeutic Drug Monitoring. 44 (4): 494–510. doi:10.1097/FTD.0000000000000970. PMID 35149665. S2CID 246776288.
- ↑ Hunger A, Kebrle J, Rossi A, Hoffmann K (1957). "Synthesis of basic substituted, analgesically active benzimidazole derivatives". Experientia. 13 (10): 400–1. doi:10.1007/BF02161116. PMID 13473817.
- ↑ US patent 2935514, Hoffman K, Hunger A, "BENZMDAZOLES (sic)", published 1960-05-03, assigned to Ciba Pharmaceutical Products Inc.
- ↑ Drug Enforcement Administration (June 2021). "Benzimidazole Opioids" (PDF). Retrieved 6 January 2022.
- ↑ Di Trana A, Pichini S, Pacifici R, Giorgetti R, Busardò FP (2022). "Synthetic Benzimidazole Opioids: The Emerging Health Challenge for European Drug Users". Frontiers in Psychiatry. 13 858234. doi:10.3389/fpsyt.2022.858234. ISSN 1664-0640. PMC 8990956. PMID 35401256.
- ↑ Kozell LB, Eshleman AJ, Wolfrum KM, Swanson TL, Bloom SH, Benware S, et al. (April 2024). "Pharmacologic Characterization of Substituted Nitazenes at μ, κ, and Δ Opioid Receptors Suggests High Potential for Toxicity". The Journal of Pharmacology and Experimental Therapeutics. 389 (2): 219–228. doi:10.1124/jpet.123.002052. PMC 11026150. PMID 38453524.
- ↑ Nielsen S, Silva JP, Jones JD, Krotulski A, Poovendran D, Muzangizi D, et al. (2026). "Behavioural Effects and Naloxone Effectiveness With New Synthetic Opioids". Drug and Alcohol Review. 45 (1) e70040. doi:10.1111/dar.70040. ISSN 1465-3362. PMC 12679901. PMID 41093771.
- ↑ Renton P, Green B, Maddaford S, Rakhit S, Andrews JS (March 2012). "NOpiates: Novel Dual Action Neuronal Nitric Oxide Synthase Inhibitors with μ-Opioid Agonist Activity". ACS Medicinal Chemistry Letters. 3 (3): 227–31. doi:10.1021/ml200268w. PMC 4025805. PMID 24900459.