Intoxications in the STRIDA project involving a panorama of psychostimulant pyrovalerone derivatives, MDPV copycats

Figures & data

Figure 1. Chemical structures of the 11 studied pyrovalerone derivatives together with the parent compounds α-PVP and MDPV.

Table 1. Monoisotopic and exact masses of monitored protonated molecular ions of the 11 pyrovalerones, together with information on their appearances as recreational drugs and classification in Sweden. Information on MDPV and α-PVP is also included for comparison.

Substance (alternative name)	Mono-isotopic mass	Exact mass (M + H^+)^+	Discussed on a Swedish Internet forum since	EU seizures reported by the EMCDDA since	Classified in Sweden since	Classified as^a
α-PPP	203.1310	204.1383	January 2009	2009	February 2013	N
4Me-PPP (MPPP)	217.1467	218.1539	August 2011	2010	January 2015	N
α-PBP	217.1467	218.1539	June 2013	2011	January 2015	N
α-PVT	237.1187	238.1260	September 2013	2013	January 2015	H
4F-α-PVP	249.1529	250.1602	September 2013	2014	January 2015	N
4Cl-α-PVP	265.1233	266.1306	August 2015	2015	August 2016	H
α-PHP (PV7)	245.1780	246.1852	May 2014	2014	January 2015	H
4F-α-PHP	263.1685	264.1758	August 2015	2015	August 2016	H
MDPHP	289.1678	290.1751	July 2014	2014	June 2015	N
PV8 (α-PEP, α-PHPP)	259.1936	260.2009	June 2013	2013	January 2015	H
4F-α-PEP (4F-PV8)	277.1842	278.1915	April 2014	2014	January 2016	H
α-PVP			August 2011	2012	February 2013	N
MDPV			September 2006	2008	February 2010	N

^a N: Narcotics; H: harmful to health.

Figure 2. Chromatograms from the analysis of α-PPP in a urine sample from one selected case of intoxication. The analysis was performed with LC–HRMS in scan mode and in MS/MS mode for identification. Comparison was made with certified reference substance.

Table 2. Urine and serum concentrations of pyrovalerone NPS in intoxication cases.

	Urine concentration (ng/mL)			Serum concentration (ng/mL)
Substance	median	range	N	median	range	N
α-PPP	13	4–102	8	–	–	0
4Me-PPP	2095	1290–2900	2	–	–	0
α-PBP	14	2–13,200	37	14	2–436	6
α-PVT	43	4–7380	11	184	8–1060	4
4F-α-PVP	48	1–24,600	17	33	23–43	2
4Cl-α-PVP	5220	–	1	–	–	0
α-PHP	68	1–300,000	11	6	4–10	3
MDPHP	34	2–5960	19	8	3–136	7
4F-α-PHP	97	11–10400	7	15	3–28	2
PV8	20	2–1270	8	–	–	0
4F-PV8	14	3–182	5	–		0

Table 3. Details of the 8 single drug intoxication cases.

	Substance concentrations, ng/mL
Substance	Serum	Urine	Creatinine in urine, mmol/L	Sampling time after admission (from drug intake)	Drug experience	Symptoms for seeking hospital	Clinical observations	Treatment	PSS
α-PBP	161	305	1.4	1 h (2 h)	Opiates, MDPV	General body pain, breathing difficulties, tingling in legs after injection	RLS 1, mild agitation, paresthesia, muscle pain, hypothermia (35.9 °C/96.6 °F)	Diazepam 5 mg iv	2
MDPHP	<1.0	48	8.2	1 h (–)	–	Thorax pain, breathing difficulties and sense of fatigue since 3 weeks	Long latency of response and speech, but tactile hypersensitive		1
MDPHP	6.7	43	12.8	2 h (4–5 h)	2 years experimental drug use	Unpleasant feelings in the thorax region	RLS 1		1
MDPHP	14.3	19	5.8	2 h (4–5 h)	2 years experimental drug use	Euphoria followed by “panic anxiety attack”, including dizziness, blurry vision, breathing difficulties, unpleasant feelings in the thorax region, cold extremities	RLS 1, hypertension (168/77 mmHg)		1
MDPHP	3.8	25	5.4	24 h (–)	Long term misuse of drugs	Psychosis, aggressiveness (police assistance needed)	Hallucinations, aggressiveness, RLS 1	Lorazepam 2.5 mg po	2
4F-α-PVP	43	–	–	Promptly (–)	Misuse of alcohol and other drugs, previously treated for intoxication related to amfetamine	Psychosis, aggressiveness (police assistance needed)	GCS 13, agitation, dilated pupils, hyperthermia (39.3 °C/102.7 °F), tachycardia (150/min), hypertension (148/130 mmHg), CRP 123 mg/L, rhabdomyolysis (S-myoglobin 455 µg/L [on admission]/3162 µg/L [22 h from arrival], P-creatinine 115 µmol/L)	Propofol, midazolam, cold fluids	3
α-PVT	425	–	–	Promptly (9 h)	–	Apathetic, anxiety	GCS 13, mild agitation, muscle spasm in the back, tachycardia (109/min), CRP 22 mg/L		2
α-PHP	1.9	3	8.1	6.5 h (7.5 h)	Misuse of drugs, previously treated for intoxication related to synthetic cannabinoids	Breathing difficulties, palpitation, jaw muscle spasm within 1 h after drug exposure	GCS 15, dilated pupils, paresthesia, hypertension (142/82 mmHg), respiratory alcalosis (pH 7.56, pCO2 3.2 kPa, standard bicarbonate 25 mmol/L)		1

–: Sample or information missing; CRP: C-reactive protein; GCS: Glasgow Coma Scale; iv: intravenous; P: plasma; po: peroral; PSS: Poisoning Severity Score; RLS: Reaction Level Scale; S: serum.

Figure 3. Quarterly statistics during 2010–2016 from the STRIDA project of analytically confirmed (in urine or serum) cases of intoxication involving a pyrovalerone derivative. The time for substance regulation in Sweden is indicated by a bold vertical line.

Table 4. Pyrovalerone substances mentioned in telephone inquiries to the Swedish Poisons Information Centre.

	Year
Substances	2012	2013	2014	2015	2016
MDPV	194	208	129	74	34
α-PVP	6	9	3	2	4
Pyrovalerones in this study	0	0	0	0	0
α-PPP	1	2	0	0	0
4Me-PPP	0	0	0	0	0
α-PBP	0	6	2	0	0
α-PVT	0	0	2	0	0
4F-α-PVP	0	0	24	0	0
4Cl-α-PVP	0	0	0	0	4
MDPHP	0	0	0	0	0
α-PHP	0	0	25	8	4
4F-α-PHP	0	0	0	1	5
PV8/α-PEP	0	0	8	3	1
4F-PV8	0	0	1	0	0
Other pyrovalerones
4Cl-α-PHP	0	0	0	0	2
3,4-MeO-α-PVP	0	0	0	1	0
3,4-MeO-α-PHP	0	0	0	5	0
5-DBFPV	0	0	0	0	1
α-PiHP	0	0	0	0	2
5-BPDi	0	0	0	0	1
PV	2	0	9	1	0