Sensorimotor Alterations Induced by Novel Fentanyl Analogs in Mice: Possible Impact on Human Driving Performances

Overview

Journal Curr Neuropharmacol

Publisher Bentham Science Publishers

Date 2022 Nov 18

PMID 36397617

Authors

Sabrine Bilel

Arianna Giorgetti

Micaela Tirri

Raffaella Arfe

Virginia Cristofori

Beatrice Marchetti

Giorgia Corli

Lorenzo Caruso

Giorgio Zauli

Raffaele Giorgetti

Matteo Marti

Affiliations

Soon will be listed here.

Abstract

Operating a vehicle is a complex task that requires multiple cognitive functions and psychomotor skills to cooperate. Driving might be impaired by licit or illicit drugs, including novel psychoactive substances (NPS) and novel synthetic opioids (NSO), the effects of which are still yet to be elucidated in humans. In the present work, a revision of the literature regarding the psychomotor impairing effects of Fentanyl (FENT) and three analogues (Acrylfentanyl, Ocfentanyl and Furanylfentanyl) is presented, as emerged by experimental studies on humans, driving under the influence of a drug (DUID) and intoxication cases. An experimental study on a mouse model evaluated the sensorimotor alterations induced by FENT and the three fentalogs. Acute systemic administration of the four opioids (0.01-15 mg/kg i.p.) dose-dependently decreased the visual object and placing tests, the acoustic and the tactile responses of mice. The preclinical data are in accordance with the data that emerged from the revision of the literature regarding experimental data on humans, driving under the influence of drugs and intoxication cases, suggesting that novel synthetic opioids might affect the psychomotor performances on daily human tasks with a particular focus on driving.

Citing Articles

Pharmaco-toxicological effects of the novel tryptamine hallucinogen 5-MeO-MiPT on motor, sensorimotor, physiological, and cardiorespiratory parameters in mice-from a human poisoning case to the preclinical evidence.

Bassi M, Bilel S, Tirri M, Corli G, Di Rosa F, Gregori A Psychopharmacology (Berl). 2024; 241(3):489-511.

PMID: 38214743 PMC: 10884077. DOI: 10.1007/s00213-024-06526-8.

Pharmaco-Toxicological Effects of Atypical Synthetic Cathinone Mephtetramine (MTTA) in Mice: Possible Reasons for Its Brief Appearance over NPSs Scene.

Corli G, Tirri M, Arfe R, Marchetti B, Bernardi T, Borsari M Brain Sci. 2023; 13(2).

PMID: 36831704 PMC: 9954072. DOI: 10.3390/brainsci13020161.

References

Zhu Y, Hsu M, Pintar J . Developmental expression of the mu, kappa, and delta opioid receptor mRNAs in mouse. J Neurosci. 1998; 18(7):2538-49. PMC: 6793117. View

Abood M, Noel M, Carter R, Harris L . Evaluation of a series of N-alkyl benzomorphans in cell lines expressing transfected delta- and mu-opioid receptors. Biochem Pharmacol. 1995; 50(6):851-9. DOI: 10.1016/0006-2952(95)02007-y. View

Tosolini A, Mohan R, Morris R . Targeting the full length of the motor end plate regions in the mouse forelimb increases the uptake of fluoro-gold into corresponding spinal cord motor neurons. Front Neurol. 2013; 4:58. PMC: 3657688. DOI: 10.3389/fneur.2013.00058. View

Lin Y, Carpenter D . Direct excitatory opiate effects mediated by non-synaptic actions on rat medial vestibular neurons. Eur J Pharmacol. 1994; 262(1-2):99-106. DOI: 10.1016/0014-2999(94)90032-9. View

Fogarty M, Papsun D, Logan B . Analysis of Fentanyl and 18 Novel Fentanyl Analogs and Metabolites by LC-MS-MS, and report of Fatalities Associated with Methoxyacetylfentanyl and Cyclopropylfentanyl. J Anal Toxicol. 2018; 42(9):592-604. DOI: 10.1093/jat/bky035. View

Logan B, DOrazio A, Mohr A, Limoges J, Miles A, Scarneo C . Recommendations for Toxicological Investigation of Drug-Impaired Driving and Motor Vehicle Fatalities-2017 Update. J Anal Toxicol. 2017; 42(2):63-68. DOI: 10.1093/jat/bkx082. View

Tonellato D, Ransohoff J, Nash C, Melanson S, Petrides A, Tolan N . Traumatic pedestrian and bicyclist injuries associated with intoxication. Am J Emerg Med. 2020; 45:192-195. PMC: 7884480. DOI: 10.1016/j.ajem.2020.08.024. View

Fishbain D, Cutler R, Rosomoff H, Rosomoff R . Are opioid-dependent/tolerant patients impaired in driving-related skills? A structured evidence-based review. J Pain Symptom Manage. 2003; 25(6):559-77. DOI: 10.1016/s0885-3924(03)00176-3. View

Bilel S, Azevedo Neto J, Arfe R, Tirri M, Gaudio R, Fantinati A . In vitro and in vivo pharmaco-dynamic study of the novel fentanyl derivatives: Acrylfentanyl, Ocfentanyl and Furanylfentanyl. Neuropharmacology. 2022; 209:109020. DOI: 10.1016/j.neuropharm.2022.109020. View

10.

Menefee L, Frank E, Crerand C, Jalali S, Park J, Sanschagrin K . The effects of transdermal fentanyl on driving, cognitive performance, and balance in patients with chronic nonmalignant pain conditions. Pain Med. 2004; 5(1):42-9. DOI: 10.1111/j.1526-4637.2004.04005.x. View

11.

Centola C, Giorgetti A, Zaami S, Giorgetti R . Effects of GHB On Psychomotor and Driving Performance. Curr Drug Metab. 2018; 19(13):1065-1072. DOI: 10.2174/1389200219666180124113802. View

12.

Vigolo A, Ossato A, Trapella C, Vincenzi F, Rimondo C, Seri C . Novel halogenated derivates of JWH-018: Behavioral and binding studies in mice. Neuropharmacology. 2015; 95:68-82. DOI: 10.1016/j.neuropharm.2015.02.008. View

13.

Ghoneim M, Mewaldt S, Thatcher J . The effect of diazepam and fentanyl on mental, psychomotor and electroencephalographic functions and their rate of recovery. Psychopharmacologia. 1975; 44(1):61-6. DOI: 10.1007/BF00421185. View

14.

Dussy F, Hangartner S, Hamberg C, Berchtold C, Scherer U, Schlotterbeck G . An Acute Ocfentanil Fatality: A Case Report with Postmortem Concentrations. J Anal Toxicol. 2016; 40(9):761-766. DOI: 10.1093/jat/bkw096. View

15.

Ivers R, Mitchell P, Cumming R . Sensory impairment and driving: the Blue Mountains Eye Study. Am J Public Health. 1999; 89(1):85-7. PMC: 1508504. DOI: 10.2105/ajph.89.1.85. View

16.

Meyer A, OKeefe J, Poort J . Two Distinct Types of Eye-Head Coupling in Freely Moving Mice. Curr Biol. 2020; 30(11):2116-2130.e6. PMC: 7284311. DOI: 10.1016/j.cub.2020.04.042. View

17.

Dumas E, Pollack G . Opioid tolerance development: a pharmacokinetic/pharmacodynamic perspective. AAPS J. 2008; 10(4):537-51. PMC: 2628209. DOI: 10.1208/s12248-008-9056-1. View

18.

Helander A, Backberg M, Beck O . MT-45, a new psychoactive substance associated with hearing loss and unconsciousness. Clin Toxicol (Phila). 2014; 52(8):901-4. DOI: 10.3109/15563650.2014.943908. View

19.

Horswill M, Plooy A . Auditory feedback influences perceived driving speeds. Perception. 2008; 37(7):1037-43. DOI: 10.1068/p5736. View

20.

Guerrieri D, Rapp E, Roman M, Thelander G, Kronstrand R . Acrylfentanyl: Another new psychoactive drug with fatal consequences. Forensic Sci Int. 2017; 277:e21-e29. DOI: 10.1016/j.forsciint.2017.05.010. View