5F-AKB48 or 5F-APINACA or 1-(5-fluoropentyl)-N-1H-indazole-3-carboxamide was first identified in March 2012. Although not much is known about the consequences of its consumption by humans, it is one of the new generation cannabinoids which is increasingly sold, whether in powder, in e-liquids for electronic cigarettes, or in blends (mixtures of different herbs).
It has a high affinity for the CB2 cannabinoid receptors, while possessing a very low affinity for the central cannabinoid CB1 receptors. Although the molecular structure differs only slightly from that of AKB48 by the addition of a fluorine atom to the terminal carbon atom of the pentyl chain, the effects are reported to be significantly more potent than those of the mother compound .
RationaleAKB48 and its fluorinate derivate 5F-AKB48 are two novel synthetic cannabinoids belonging to a structural class with an indazole core structure. They are marketed as incense, herbal preparations or chemical supply for their psychoactive Cannabis-like effects. Objectives The present study was aimed at investigating the in vitro and in vivo pharmacological activity of AKB48 and 5F-AKB48 in male CD-1 mice and comparing their in vivo effects with those caused by the administration of Δ9-THC and JWH-018. ResultsIn vitro competition binding experiments performed on mouse and human CB1 and CB2 receptors revealed a nanomolar affinity and potency of the AKB48 and 5F-AKB48. In vivo studies showed that AKB48 and 5F-AKB48, induced hypothermia, increased pain threshold to both noxious mechanical and thermal stimuli, caused catalepsy, reduced motor activity, impaired sensorimotor responses (visual, acoustic and tactile), caused seizures, myoclonia, hyperreflexia and promoted aggressiveness in mice.
Moreover, microdialysis study in freely moving mice showed that systemic administration of AKB48 and 5F-AKB48 stimulated dopamine release in the nucleus accumbens. Behavioural, neurological and neurochemical effects were fully prevented by the selective CB1 receptor antagonist/inverse agonist AM 251. Conclusions For the first time, the present study demonstrates the overall pharmacological effects induced by the administration of AKB48 and 5F-AKB48 in mice and suggests that the fluorination can increase the power and/or effectiveness of SCBs. Furthermore, this study outlines the potential detrimental effects of SCBs on human health.
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