In vitro and in vivo pharmaco-dynamic study of the novel fentanyl derivatives: Acrylfentanyl, Ocfentanyl and Furanylfentanyl

Bilel, Sabrine; Neto, Joaquim Azevedo; Arfè, Raffaella; Tirri, Micaela; Maria, Gaudio Rosa; Fantinati, Anna; Bernardi, Tatiana; Boccuto, Federica; Marchetti, Beatrice; Corli, Giorgia; Serpelloni, Giovanni; De-Giorgio, Fabio; Malfacini, Davide; Trapella, Claudio; Girolamo, Calo’; Marti, Matteo

doi:10.1016/j.neuropharm.2022.109020

Cited by 23 publications

(14 citation statements)

References 84 publications

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“…To monitor the cardiorespiratory parameters in awake and freely moving animals, without using invasive instruments and handling, a collar with a sensor was used to detect heart rate, breath rate, oxygen saturation, and pulse distension with an acquisition frequency of 15 Hz [ 28 , 125 , 126 , 127 , 128 ]. During experiment, mice were allowed to freely move around their cages (30 × 30 × 20 cm), while having no access to food or water and while being monitored by the sensor collar through the software MouseOx Plus (STARR Life Sciences ® Corp, Oakmont, PA, USA).…”

Section: Methodsmentioning

confidence: 99%

The Old and the New: Cardiovascular and Respiratory Alterations Induced by Acute JWH-018 Administration Compared to Δ9-THC—A Preclinical Study in Mice

Marchetti

Bilel

Tirri

et al. 2023

IJMS

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Several new psychoactive substances (NPS) are responsible for intoxication involving the cardiovascular and respiratory systems. Among NPS, synthetic cannabinoids (SCs) provoked side effects in humans characterized by tachycardia, arrhythmias, hypertension, breathing difficulty, apnoea, myocardial infarction, and cardiac arrest. Therefore, the present study investigated the cardio-respiratory (MouseOx Plus; EMKA electrocardiogram (ECG) and plethysmography TUNNEL systems) and vascular (BP-2000 systems) effects induced by 1-naphthalenyl (1-pentyl-1H-indol-3-yl)-methanone (JWH-018; 0.3–3–6 mg/kg) and Δ9-tetrahydrocannabinol (Δ9-THC; 0.3–3–6 mg/kg), administered in awake CD-1 male mice. The results showed that higher doses of JWH-018 (3–6 mg/kg) induced deep and long-lasting bradycardia, alternated with bradyarrhythmia, spaced out by sudden episodes of tachyarrhythmias (6 mg/kg), and characterized by ECG electrical parameters changes, sustained bradypnea, and systolic and transient diastolic hypertension. Otherwise, Δ9-THC provoked delayed bradycardia (minor intensity tachyarrhythmias episodes) and bradypnea, also causing a transient and mild hypertensive effect at the tested dose range. These effects were prevented by both treatment with selective CB1 (AM 251, 6 mg/kg) and CB2 (AM 630, 6 mg/kg) receptor antagonists and with the mixture of the antagonists AM 251 and AM 630, even if in a different manner. Cardio-respiratory and vascular symptoms could be induced by peripheral and central CB1 and CB2 receptors stimulation, which could lead to both sympathetic and parasympathetic systems activation. These findings may represent a starting point for necessary future studies aimed at exploring the proper antidotal therapy to be used in SCs-intoxicated patient management.

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Section: Methodsmentioning

confidence: 99%

The Old and the New: Cardiovascular and Respiratory Alterations Induced by Acute JWH-018 Administration Compared to Δ9-THC—A Preclinical Study in Mice

Marchetti

Bilel

Tirri

et al. 2023

IJMS

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“…The effects of AKB48 were evaluated using a series of behavioural tests (visual object and visual placing response test, acoustic test, tactile test, tail pinch test, core temperature test, breath rate test, and mobility time test) routinely used in our laboratories to describe the effects of synthetic cannabinoids in mice (Bilel et al, 2020;Canazza et al, 2016Canazza et al, , 2017Ossato et al, 2015Ossato et al, , 2016Vigolo et al, 2015) and widely validated for the preclinical characterization of the pharmacotoxicological effects of NPSs in rodents (Arfè et al, 2021;Bilel et al, 2021Bilel et al, , 2022De-Giorgio et al, 2020;Ossato et al, 2018;Tirri et al, 2022).…”

Section: Behavioural Studiesmentioning

confidence: 99%

Sex‐specific behavioural, metabolic, and immunohistochemical changes after repeated administration of the synthetic cannabinoid AKB48 in mice

Corli,

Roda,

Tirri

et al. 2024

British J Pharmacology

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Background and PurposeAKB48 is a synthetic cannabinoid illegally sold for its psychoactive cannabis‐like effects that has been associated to several acute intoxications and which effects are poorly known.Experimental ApproachUsing a behavioural, neurochemical and immunohistochemical approach we investigated the pharmaco‐toxicological effects, plasma pharmacokinetic and neuroplasticity at cannabinoid CB1 receptor (CB1R) in the cerebellum and cortex induced by repeated AKB48 administration in male and female mice.Key ResultsThe effects of AKB48 varied significantly depending on sex and length of treatment. The 1st injection impaired sensorimotor responses and reduced body temperature, analgesia, and breath rate at a greater extent in females than in males, the 2nd injection induced stronger effects in males while the 3rd injection of AKB48 induced weaker responses in both sexes, suggesting the emergence of tolerance. The CB1R antagonist NESS‐0327 prevented the effects induced by repeated AKB48, confirming a CB1R‐mediated action of the drug.Blood AKB48 levels were higher in females than in males and repeated administration caused a progressive rise of AKB48 content in blood samples of both sexes, suggesting an inhibitory effect on cytochrome activity. Finally, immunohistochemical analysis revealed higher expression of CB1Rs in the cerebellum and cortex of females, and a rapid CB1R downregulation in cerebellar and cortical areas following repeated AKB48 injections, with neuroadaptation occurring generally more rapidly in females than in males.Conclusion and ImplicationsWe showed for the first time that AKB48 effects significantly vary with prolonged use and that sex affects the pharmacodynamic/pharmacokinetic responses to its repeated administration, suggesting a sex‐tailored approach in managing AKB48‐induced intoxication.

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“…Látka byla získána za účelem získání opioidu s vyšším terapeutickým indexem v porovnání s fentanylem. V molekule ocfentanilu byla propionamidová skupina fentanylu nahrazena methoxyacetamidem a byla provedena adice fluoru na N-fenylový kruh 17 . Klinické studie analgetické aktivity u myší potvrdily cca 2,5× vyšší účinnost oproti fentanylu.…”

Section: Ocfentanilunclassified

Orientation Test for the Presence of Fentanyl Derivatives by Thin-Layer Chromatography

Jelínková¹,

Moravcová²,

Žuja³

2023

Chem. Listy

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The article contains information on the properties of fentanyl derivatives and a method for their simple orientation identification. Thin-layer chromatography (TLC) was deliberately chosen to perform the experiment because it is the most suitable method for rapid analysis of the collected sample under the conditions of the field chemical laboratory operated by the Army of the Czech Republic. On the basis of the experimental work performed, it was found that the most suitable system for the identification of the fentanyl derivatives of interest by TLC is a system where the stationary phase consists of "alumina 60 F254 neutral" and the mobile phase is comprised of ethyl acetate and hexane in a ratio of 7:3. The findings are fully usable in practice and will be included in the standard operating procedures for the determination of these types of substances in the Field Transport Chemical Laboratory PPCHL-AL2/ch, most likely in the form of a certified methodology.

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In vitro and in vivo pharmaco-dynamic study of the novel fentanyl derivatives: Acrylfentanyl, Ocfentanyl and Furanylfentanyl

Cited by 23 publications

References 84 publications

The Old and the New: Cardiovascular and Respiratory Alterations Induced by Acute JWH-018 Administration Compared to Δ9-THC—A Preclinical Study in Mice

The Old and the New: Cardiovascular and Respiratory Alterations Induced by Acute JWH-018 Administration Compared to Δ9-THC—A Preclinical Study in Mice

Sex‐specific behavioural, metabolic, and immunohistochemical changes after repeated administration of the synthetic cannabinoid AKB48 in mice

Orientation Test for the Presence of Fentanyl Derivatives by Thin-Layer Chromatography

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