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- Title
MAM-2201 acute administration impairs motor, sensorimotor, prepulse inhibition, and memory functions in mice: a comparison with its analogue AM-2201.
- Authors
Corli, Giorgia; Tirri, Micaela; Bilel, Sabrine; Arfè, Raffaella; Coccini, Teresa; Roda, Elisa; Marchetti, Beatrice; Vincenzi, Fabrizio; Zauli, Giorgio; Borea, Pier Andrea; Locatelli, Carlo Alessandro; Varani, Katia; Marti, Matteo
- Abstract
Rationale: 1-[(5-fluoropentyl)-1H-indol-3-yl](4-methyl-1-naphthalenyl) methanone (MAM-2201) is a potent synthetic cannabinoid receptor agonist illegally marketed in "spice" products and as "synthacaine" for its psychoactive effects. It is a naphthoyl-indole derivative which differs from its analogue 1-[(5-Fluoropentyl)-1H-indol-3-yl](1-naphthylenyl) methanone (AM-2201) by the presence of a methyl substituent on carbon 4 (C-4) of the naphthoyl moiety. Multiple cases of intoxication and impaired driving have been linked to AM-2201 and MAM-2201 consumption. Objectives: This study aims to investigate the in vitro (murine and human cannabinoid receptors) and in vivo (CD-1 male mice) pharmacodynamic activity of MAM-2201 and compare its effects with those induced by its desmethylated analogue, AM-2201. Results: In vitro competition binding studies confirmed that MAM-2201 and AM-2201 possess nanomolar affinity for both CD-1 murine and human CB1 and CB2 receptors, with preference for the CB1 receptor. In agreement with the in vitro binding data, in vivo studies showed that MAM-2201 induces visual, acoustic, and tactile impairments that were fully prevented by pretreatment with CB1 receptor antagonist/partial agonist AM-251, indicating a CB1 receptor mediated mechanism of action. Administration of MAM-2201 also altered locomotor activity and PPI responses of mice, pointing out its detrimental effect on motor and sensory gating functions and confirming its potential use liability. MAM-2201 and AM-2201 also caused deficits in short- and long-term working memory. Conclusion: These findings point to the potential public health burden that these synthetic cannabinoids may pose, with particular emphasis on impaired driving and workplace performance.
- Subjects
NEURAL inhibition; CANNABINOID receptors; SYNTHETIC receptors; SYNTHETIC marijuana; LONG-term memory; SHORT-term memory; TROPANES
- Publication
Psychopharmacology, 2023, Vol 240, Issue 7, p1435
- ISSN
0033-3158
- Publication type
Article
- DOI
10.1007/s00213-023-06378-8