Table 2.

List of NPS identified for the first time by NPSfinder® from January to August 2020.

NPS	Chemical family	Chemical name	Description	Previously unidentified NPS	NPSfinder® identification date
3M-4F-αPVP	Catinones	1-(4-fluoro-3-methylphenyl)-2-(pyrrolidin-1-yl)pentan-1-one	It is the 3-methyl derivative of 4F-alpha-PVP. Cathinones, which are structurally like 4F-α-PVP, cross the brain-blood barrier effectively (43). No information has been retrieved on its mechanism of action, but it is likely to affect the monoaminergic system, particularly the dopamine transport, as the 4F-PVP. It is a stimulant.	N	23/07/2020
4H-CMC	Cathinones	N.a.	Derivative of 4-CMC s a stimulant drug of the cathinone class.	Y	06/05/2020
MD-PEP/MD-PV8	Cathinones	1-(benzo[d][1,3]dioxol-5-yl)-2-(pyrrolidin-1-yl)heptan-1-one	MDPEP is a stimulant of the Cathinone class, which has been reported as a novel designer drug (44). MD-PEP is the methylendioxy derivative of α-PEP and the higher homolog of α-pyrrolidinohexiophenone (α-PHP), having an extra carbon on the alkyl side chain. No in vitro studies are available to assess the activity on the brain but based on previous work the longer alkyl chain may increase its potency (45).	N	06/05/2020
EBK-EBDP	Cathinones	N.a.	EBK-EBDP is probably a mixture of EBK, a new synthetic derivative of βk-EBDP/ephylone, and ephylone itself. On the website where the molecule was first identified by the NPSfinder®, C20H27FN2O3 was the molecular formula reported. The description was then changed to EBK alone. Other chemical formulas are available online for the same compound. It is sold as a potential strong stimulant with powerful psychotic effects.	Y	06/05/2020
HEP	Cathinones	N.a.	HEP belongs to cathinone and amphetamine chemical classes and it is the new HEX-EN replacement.	Y	06/05/2020
A-PCYP	Cathinones	2-cyclohexyl-1-phenyl-2-(pyrrolidin-1-yl)ethanone	A-PCYP is a stimulant drug of the cathinone class that has been sold online as a designer drug. In a series of α-substituted pyrrolidinyl cathinone derivatives developed in 2015, the α-cyclopentyl derivative was found to have around the same potency in vitro as an inhibitor of the dopamine transporter as the α-propyl derivative a-PVP, while the α-cyclohexyl derivative α-PCYP was around twice as strong (46).	Y	06/03/2020
4F-MDMB-BICA	Cannabimimetics	Methyl 2-[[1-(4-fluorobutyl)indole-3-carbonyl]amino]-3,3-dimethyl-butanoate	4F-MDMB-BICA is a synthetic cannabinoid structurally similar to 4F-MDMB-BINACA and 5F-MDMB-PICA. 5F-MDMB-PICA is explicitly a Schedule I substance in the United States; 4F-MDMB-BICA is not a scheduled substance (47).	N	23/07/2020
5F-NPB-22	Cannabimimetics	1-(5-fluoropentyl)-8-quinolinyl ester-1H-indazole-3-carboxylic acid	5-F-NPB-22 is an analog of NPB-22 that differs by adding a fluorine atom to the terminal carbon of the alkyl chain (48).	Y	13/06/2020
ETAZENE	Opioids	(2-[(4-ethoxyphenyl)methyl]-N,N-diethyl-1H-benzimidazole-1-ethanamine)	Etazene was notified as an NPS on 1 June 2020 by Poland (49). The substance belongs to the 2-benzylbenzimidazole group of synthetic opioid analgesics; It is less potent than isonitazene but still almost 70 time more potent than morphine (50, 51).	N	23/07/2020
METODESNITAZENE	Opioids	N,N-diethyl-2-(2-(4-methoxybenzyl)-1H-benzo[d]imidazol-1-yl)ethan-1-amine;	Metodesnitazene is a 2-benzylbenzimidazole. It is structurally related to etonitazene (Schedule I of the 1961 United Nations Single Convention on Narcotic Drugs), with the presence of an ethoxy group instead of the methoxy and the absence of the nitro group at the 5 position. The analgesic activity of the 2-benzylbenzimidazole appears to be related to the substitution at the benzyl moiety with para substitution showing higher activity (52).	N	23/07/2020
FLUNITAZENE	Opioids	N,N-diethyl-2-[(4-fluorophenyl)methyl]-5-nitro-1H-benzimidazole-1-ethanamine	It is a novel opioid of the 5-nitro-2-benzylbenzimidazole family that shares the same structure as Clonitazene but with a fluorine atom instead of the chlorine in para to the phenyl ring.	Y	23/05/2020
BRORPHINE	Opioids	1-[1-[1-(4-bromophenyl)ethyl]-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one	Brorphine is a piperidine benzimidazolone (3-piperidin-4-yl-1H-benzimidazol-2-one). It shares structural similarities with the internationally controlled narcotic analgesic bezitramide and with the benzimidazole opioids isotonitazene and etazene. However, the latter cannot be considered close derivatives (49).	N	18/03/2020
DIPHENPIPENOL	Opioids	3-[2-[4-(2-methoxyphenyl) piperazin-1-yl]-2-phenylethyl]phenol	Diphenpipenol was invented in the 1970s by Dainippon Pharmaceutical Co (53). It is an opioid analgesic, derivative of 1-substituted-4-(1,2-diphenylethyl)piperazines. It is related to MT-45 and AD-1211, being the most potent compound in the series. The (S) isomer has 105 times the potency of morphine in animal studies (54). This makes it a similar strength to fentanyl and consequently diphenpipenol can be considered a threat to life expected to cause respiratory depression, sedation, itching, nausea and vomiting upon consumption.	Y	20/08/2020
NORTILIDINE	Opioids	ethyl-2-(methylamino)-1-phenylcyclohex-3-ene-1-carboxylate	Nortilidine is the major demethylated active metabolite of tilidine. The racemate has opioid analgesic effects roughly equivalent in potency to that of morphine (55). The drug also acts as a dopamine reuptake inhibitor (26).	N	20/08/2020
3-CL-PCP	PCP-like	1-[1-(3-Chlorophenyl )cyclohexyl]piperidine	3-Chlorophencyclidine (3-CL-PCP) is a dissociative anesthetic drug with hallucinogenic and sedative effects that has been sold as a research chemical. It has comparable potency to phencyclidine but slightly different effects. This is due to its altered binding profile at various targets, particularly being somewhat more potent as an NMDA antagonist while having around the same potency as a dopamine reuptake inhibitor.	Y	23/07/2020
3-F-PCP	PCP-like	1-[1-(3-Fluorophenyl) cyclohexyl]piperidine	3-F-PCP is a dissociative hallucinogen of the aryl cyclohexylamine class related to phencyclidine (PCP) which has been sold online as a designer drug. It is the fluorinated analog of the 3-MeO-PCP, substance listed in UK as Class B of the Misuse of Drugs Act (1971). No in vitro studies have been found for this compound but due to the similarity with 3-MeO-PCP it should act acts mainly as an NMDA receptor antagonist interacting with the sigma σ1 receptor and the serotonin transporter as well.	Y	23/07/2020
1F-LSD	Hallucinogens	(6aR,9R)-9-(diethylcarbamoyl)-7-methyl-6a,7,8,9-tetrahydroindolo[4,3-fg]quinoline-4(6H)-carboxylic acid	1-formyl-lysergic acid diethylamide is a chemical analog of ALD-52, which is a formyl group on position 1 instead of an acetyl. No information on potency is available.	Y	23/07/2020
5-CHLORO-DMT	Tryptamines	2-(5-Chloro-1H-indol-3-yl)-N,N-dimethylethan-1-amine	5-chloro-N,N-dimethyltryptamine is a novel, naturally occurring tryptamine found in certain species of deep marine sea sponges, including Smenospongia aurea and Smenospongia echina. It is closely related to 5-bromo-DMT. It was assayed for the in vitro serotonin binding receptors. It showed high nanomolar affinity to several serotonin receptors subtype. The highest affinity was observed	N	03/08/2020