EDITORIAL
Designer Drug (DD) abuse in Poland; a review of the psychoactive and toxic properties of substances found from seizures of illegal drug products and the legal consequences thereof. Part II – Piperazines/Piperidines, Phenylethylamines, Tryptamines and miscellaneous ‘Others’
 
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1
Chief Sanitary Inspectorate, Warsaw, Poland
2
Institute of Haematology and Transfusion Medicine, Warsaw, Poland
3
Independent Laboratory of Molecular Biology, Institute of Rural Health, Lublin, Poland
4
Department of Public Health, University of Information Technology and Management, Rzeszow, Poland
5
Department of Mother and Child Health, University of Medical Sciences, Poznan, Poland
6
Department of Higiene, Chair of Social Medicine, University of Medical Sciences, Poznan, Poland
 
Ann Agric Environ Med. 2012;19(4):871–882
KEYWORDS
ABSTRACT
As the second and concluding part, this paper continues the summary review of the scientific evidence obtained from the literature and focuses on the remaining 4/6 groupings of DDs identified in illegal products found in the huge drug seizures made recently in Poland. They consist of piperazines/piperidines, phenylethylamines, tryptamines, (briefly mentioned), and a miscellaneous ‘others’ category; cannabinoids and cathinones derivatives having being reviewed in the first part. Also included in the introduction and discussion sections, in both reviews, are some legal aspects variously interwoven with the science. It is thus intended that these two articles may help suitable legislation to be rapidly devised to make the prohibition of DDs permanent whenever deemed necessary, as well as providing an up-to-date reference source for those engaged in the DD issue; whether scientists or regulatory bodies.
 
REFERENCES (190)
1.
Kapka-Skrzypczak L, Kulpa P, Sawicki K, Cyranka M, Wojtyla A, Kruszewski M. Legal highs – legal aspects and legislative solutions. Ann Agric Environ Med. 2011; 18(2): 304-9.
 
2.
Arbo MD, Bastos ML, Carmo HF. Piperazine compounds as drugs of abuse. Drug Alcohol Depend. 2012; 122(3): 174-85.
 
3.
Bossong MG, Brunt TM, Van Dijk JP, Rigter SM, Hoek J, Goldschmidt HMJ, et al. mCPP: an undesired addition to the ecstasy market. J Psychopharmacol. 2010; 24: 1395-1401.
 
4.
Cohen BM, Butler R. BZP-party pills: a review of research on benzyl-piperazine as a recreational drug. Int J Drug Policy 2011; 22(2A): 95-101.
 
5.
Davies S, Wood DM, Smith G, Button J, Ramsey J, Archer R, et al. Purchasing ‘legal highs’ on the Internet – is there consistency in what you get? QJM 2010;103: 489-493.
 
6.
Byrska B, Zuba D, Stanaszek R. Determination of piperazine derivatives in ‘legal highs’. Problems of Forensic Sci. 2010; 31: 101-113.
 
7.
Dargan PI, Wood DM. Novel and emerging recreational drugs. Toxicol Lett. 2010; 196, (Suppl1) S16, Abstracts of the XII International Congress of Toxicology, July 19-23, 2010, Barcelona, Spain.
 
8.
Hillebrand J, Olszewski D, Sedefov R. Legal highs on the Internet. Subst Use Misuse 2010; 45(3): 330-40.
 
9.
Biliński P, Kapka-Skrzypczak L, Jabłoński P. Determining the scale of designer drugs (DD) abuse and risk to public health in Poland through an epidemiological study in adolescents. Ann Agric Environ Med. 2012; 19(3): 357-64.
 
10.
Wood DM, Davies S, Puchnarewicz M, Button J, Archer R, Ovaska H et al. Recreational use of mephedrone (4-methylmethcathinone, 4-MMC) with associated sympathomimetic toxicity. J Med Toxicol. 2010; 6(3): 327-30.
 
11.
Brandt SD, Sumnall HR, Measham, Cole J. Analyses of second-generation ‘legal highs’ in the UK: initial ndings. Drug Test Anal. 2010; 2(8): 377-82.
 
12.
Anysz W, Kusmirek R, Nosarzewska M, Raczak A, Rogowska E, Srebrzynska K, et al. Benzylopiperazyna i jej pochodne w dopalaczach. Bromat Chem Toksykol. 2010; 3: 228-232.
 
13.
Craig JC, Young RJ. 1-benzylpiperazine. Organic Syntheses Coll. 1973; 5: 88-91.
 
14.
Johnstone AC, Lea RA, Brennan KA, Schenk S, Kennedy MA, Fitzmaurice PS. Review: Benzylpiperazine: a drug of abuse? J Psychopharmacol. 2010; 21: 888-894.
 
15.
Staack RF. Piperazine designer drugs of abuse. Lancet 2007; 369(9571): 1411-3.
 
16.
Barroso M, Costa S, Dias M, Vieira DN, Queiroz JA, Lopez-Rivadulla M. Analysis of phenylpiperazine-like stimulants in human hair as trimethylsilyl derivatives by gas chromatography-mass spectrometry. J Chromatogr A. 2010; 1217(40): 6274-80.
 
17.
Wohlfarth A, Weinmann W, Dresen S. LC-MS/MS screening method for designer amphetamines, tryptamines, and piperazines in serum. Anal Bioanal Chem. 2010; 396(7): 403-14.
 
18.
Brennan KA, Lake B, Hely LS, Jones K, Gittings D, Colussi-Mas J, et al. N-benzylpiperazine has characteristics of a drug of abuse. Behav Pharmacol. 2007; 18(8): 785-90.
 
19.
Fantegrossi WE, Winger G, Woods JH, Woolverton WL, Coop A. Reinforcing and discriminative stimulus effects of 1-benzylpiperazine and trifluoromethylphenylpiperazine in rhesus monkeys. Drug Alcohol Depend. 2005; 77(2): 161-8.
 
20.
Hashimoto K, Maeda H, Goromaru T. Effects of benzylpiperazine derivatives on the neurotoxicity of 3,4-methylenedioxymeth-amphetamine in rat brain. Brain Res. 1992; 590(1-2): 41-4.
 
21.
Murphy M, Antia U, Chang HY, Han JY, Ibrahim U, Tingle M, et al. Party pills and drug-drug interactions. N Z Med J. 2009; 122(1293): 3564.
 
22.
Aitchison LK, Hughes RN. Treatment of adolescent rats with 1-benzylpiperazine: a preliminary study of subsequent behavioral effects. Neurotoxicol Teratol. 2006; 28(4): 53-8.
 
23.
Hammond KAB. Recreational drug using behaviour and legal benzylpiperazine pills. Thesis: Victoria University of Wellington, 2008. 1-279 esearcharchive.vuw.ac.nz/bitst... (access: 2012.02.16).
 
24.
The Medicines and Healthcare products Regulatory Agency (MHRA). Press release; Benzylpiperazine (PEP) pills are dangerous and illegal; 2007. http://www.mhra.gov.uk/NewsCen... (access: 2012.02.16).
 
25.
Pieszkowski W, Florek E. Dopalacze. Przegl Lek. 2009; 66: 861-865.
 
26.
King LA, Nutt D. Seizures in a night club. Lancet 2007; 370(9583) :220.
 
27.
Wood DM, Dargan PI, Button J, Holt DW, Ovaska H, Ramsey J, et al. Collapse, reported seizure – and an unexpected pill. Lancet 2007; 369(9571): 1490.
 
28.
Thompson I, Williams G, Aldington S, Williams M, Caldwell B, Dickson S, et al. The benzylpiperazine (BZP) / trifluoromethylphenylpiperazine (TFMPP) and alcohol safety study. Report to the NZ Ministry of Health; 2006. http://www.ndp.govt.nz/moh.nsf.... (access: 2012.03.02).
 
29.
Conners GP. Piperazine neurotoxicity: worm wobble revisited. J Emerg Med. 1995; 13(3): 341-3.
 
30.
The Expert Advisory Committee on Drugs (EACD) Advice to the Minister (NZ) on Benzylpiperazine (BZP); 2004: 1-10. http://www.erowid.org/chemical... (access: 2012.02.11).
 
31.
Advisory Council for the Misuse of Drugs (ACMD). Control of 1-benzylpiperazine (BZP) and related compounds; 2008: 1-19. http://www.homeo ce.gov.uk/acmd1/ACMD-BZP-Repor... (access: 2012.01.14).
 
32.
Wada M, Yamahara K, Ikeda R, Kikura-Hanajiri R, Kuroda N, Nakashima K. Simultaneous determination of N-benzylpiperazine and 1-(3-trifluoromethylphenyl)piperazine in rat plasma by HPLC-fluorescence detection and its application to monitoring of these drugs. Biomed Chromatogr. 2012; 26(1): 21-5.
 
33.
de Boer D, Bosman IJ, Hidvegi E, Manzoni C, Benko AA, dos Reys LJ, et al. Piperazine-like compounds: a new group of designer drugs-of-abuse on the European market. Forensic Sci Int. 2001; 121(1-2): 47-56.
 
34.
Staack RF, Maurer HH. Toxicological detection of the new designer drug 1-(4-methoxyphenyl)piperazine and its metabolites in urine and differentiation from an intake of structurally related medicaments using gas chromatography-mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2003; 798(2): 333-42.
 
35.
Ottaviano S, Giannotti F, Cortesi F. The effect of niaprazine on some common sleep disorders in children. A double-blind clinical trial by means of continuous home-videorecorded sleep. Childs Nerv Syst. 1991; 7(6): 332-5.
 
36.
Scherman D, Hamon M, Gozlan H, Henry JP, Lesage A, Masson M, et al. Molecular pharmacology of niaprazine. Prog Neuropsychopharmacol Biol Psychiatry 1988; 12(6): 989-1001.
 
37.
Keane PE, Strolin M, Benedetti M, Dow J. The effect of niaprazine on the turnover of 5-hydroxytryptamine in the rat brain. Neuropharmacology 1982; 21(2): 163-9.
 
38.
Lecompte Y, Roussel O, Perrin M. 1-benzylpiperazine (BZP) and 1-(3-tri-uoromethylphenyl)piperazine (TFMPP): emergence of two agents which lead to misuse. Ann Pharm Fr. 2008; 66(2): 85-91.
 
39.
Lin JC, Jan RK, Lee H, Jensen MA, Kydd RR, Russell BR. Determining the subjective and physiological effects of BZP combined with TFMPP in human males. Psychopharmacology (Berl) 2011; 214(3): 761-8.
 
40.
Robertson DW, Bloomquist W, Wong DT, Cohen ML. mCPP but not TFMPP is an antagonist at cardiac 5HT3 receptors. Life Sci. 1992; 50(8): 599-605.
 
41.
Baumann MH, Clark RD, Budzynski AG, Partilla JS, Blough BE, Rothman RB. Effects of “Legal X” piperazine analogs on dopamine and serotonin release in rat brain. Ann N Y Acad Sci. 2004; 1025: 189-97.
 
42.
Fletcher PJ, Ming ZH, Zack MH, Coscina DV. A comparison of the effects of the 5-HT1 agonists TFMPP and RU 24969 on feeding following peripheral or medial hypothalamic injection. Brain Res. 1992; 580(1-2): 265-72.
 
43.
Kant GJ, Meininger GR, Maughan KR, Wright WL, Robinson TN 3rd, Neely TM Effects of the serotonin receptor agonists 8-OH-DPAT and TFMPP on learning as assessed using a novel water maze. Pharmacol Biochem Behav. 1996; 53(2): 385-90.
 
44.
Yarosh HL, Katz EB, Coop A, Fantegrossi WE. MDMA-like behavioral effects of N-substituted piperazines in the mouse. Pharmacol Biochem Behav. 2007; 88(1): 18-27.
 
45.
Thompson I, Williams G, Caldwell B, Aldington S, Dickson S, Lucas, N, et al. Randomised double-blind, placebo-controlled trial of the effects of the ‘party pills’ BZP/TFMPP alone and in combination with alcohol. J Psychopharmacol. 2010; 24: 1299–1308.
 
46.
Wood DM, Button J, Lidder S, Ramsey J, Holt DW, Dargan P. Dissociative and sympathomimetic toxicity associated with recreational use of 1-(3-trifluoromethylphenyl) piperazine (TFMPP) and 1-benzylpiperzine (BZP). J Med Toxicol. 2008; 4(4): 254-7.
 
47.
Lee H, Kydd RR, Lim VK, Kirk IJ, Russell BR. Effects of trifluoromethylphenylpiperazine (TFMPP) on interhemispheric communication. Psychopharmacology (Berl) 2011; 213(4): 707-14.
 
48.
Schep LJ, Slaughter RJ, Vale JA, Beasley DM, Gee P. The clinical toxicology of the designer “party pills” benzylpiperazine and trifluoromethylphenylpiperazine. Clin Toxicol. 2011; 49(3): 131-41.
 
49.
Robbins TW. Relationship between reward-enhancing and stereotypical effects of psychomotor stimulant drugs. Nature 1976; 264(5581): 57-9.
 
50.
Wood DW, Puchnarewicz M, Johnston A, Dargan PI. A case series of individuals with analytically confirmed acute diphenyl-2-pyrrolidinemethanol (D2PM) toxicity. Eur J Clin Pharmacol. 2012; 68(4): 349-53.
 
51.
Lidder S, Dargan P, Sexton M, Button J, Ramsey J, Holt D, et al. Cardiovascular toxicity associated with recreational use of diphenylprolinol (diphenyl-2-pyrrolidinemethanol [D2PM]). J Med Toxicol. 2008; 4(3): 167-9.
 
52.
Kaizaki A, Tanaka S, Tsujikawa K, Numazawa S, Yoshida T. Recreational drugs, 3,4-Methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA) and diphenylprolinol, inhibit neurite outgrowth in PC12 cells. J Toxicol Sci. 2010; 35(3): 375-81.
 
53.
Yamamoto T, Kaizaki A, Tanaka S, Yoshida T. Effects of recreational drugs on neurite outgrowth in PC12 cells. Toxicol Lett. 2010; 196(Supl): S137.
 
54.
De Paoli G, Brandt SD, Pounder DJ. Analytical characterization and rapid determination of 2-(diphenylmethyl)pyrrolidine in blood and application to an internet product. J Chromatogr B Analyt Technol Biomed Life Sci. 2011; 879(31): 3771-4.
 
55.
Ferris RM, Tang FL. Comparison of the effects of the isomers of amphetamine, methylphenidate and deoxypipradrol on the uptake of l- [3H]norepinephrine and [3H]dopamine by synaptic vesicles from rat whole brain, striatum and hypothalamus J. Pharmacol. Exp. Ther. 1979; 210 :422.
 
56.
Enyedy IJ, Sakamuri S, Zaman WA, Johnson KM, Wang S. Pharmacophore-based discovery of substituted pyridines as novel dopamine transporter inhibitors. Bioorg Med Chem Lett. 2003; 13(3): 513-7.
 
57.
Stasch JP, Russ H, Schacht U, Witteler M, Neuser D, Gerlach M, et al. 4,4-Diphenylpiperidine derivates and their sila analogues. A comparative study of their interaction with neural receptor biding sites and synaptosomal monoamine uptake. Arzneimittelforschung 1988; 38(8): 1075-8.
 
58.
Nodine JH, Bodi T, Slap J, Levy HA, Siegler PE. Preliminary trial of a new stimulant SCH 5472 in ambulatory patients with depression, exhaustion, or hypersomnia syndrome. Antibiotic Med Clin Ther. 1960; 7: 771-6.
 
59.
Isbell H, Chrusciel TS. Dependence Liability of Non-Narcotic Drugs. Bull World Health Organ 1970; 43: Suppl:76-77.
 
60.
Hoffmann K, Heer J. Substituted 2-diphenylmethyl-piperadine compounds. US Patent 1960; 2: 957,879.
 
61.
Schmitt KC, Zhen J, Kharkar P, Mishra M, Chen N, Dutta AK, et al. Interaction of cocaine-, benztropine-, and GBR12909-like compounds with wild-type and mutant human dopamine transporters: molecular features that differentially determine antagonist-binding properties. J Neurochem. 2008; 107(4): 928-40.
 
62.
Davidson C, Ramsey J. Desoxypipradrol is more potent than cocaine on evoked dopamine efflux in the nucleus accumbens. J Psychopharmacol. 2012; 26(7): 1036-41.
 
63.
ACMD. Consideration of Desoxypipradrol (2-DPMP) and related pipradrol compounds; 2011. http://www.homeoffice.gov.uk/p... (access: 2012.03.01).
 
64.
Freeman S, Alder JF. Arylethylamine psychotropic recreational drugs: a chemical perspective. Eur J Med Chem. 2002; 37(7): 527-39.
 
65.
Montgomery T, Buon C, Eibauer S, Guiry PJ, Keenan AK, McBean GJ. Comparative potencies of 3,4-methylenedioxymethamphetamine (MDMA) analogues as inhibitors of [3H]noradrenaline and [3H]5-HT transport in mammalian cell lines. Br J Pharmacol. 2007; 152(7): 1121-30.
 
66.
Quinteros-Munoz D, Saez-Briones P, Diaz-Veliz G, Mora-Gutierrez S, Rebolledo Fuentes M, Cassels BK. Behavioral pro les in rats distinguish among “ecstasy,” methamphetamine and 2,5-dimethoxy-4-iodoamphetamine: Mixed effects for “ecstasy” analogues. Behav Neurosci. 2010; 124(5): 662-76.
 
67.
Bruhn JG, El-Seedi HR, Stephanson N, Beck O, Shulgin AT. Ecstasy analogues found in cacti. J Psychoactive Drugs 2008; 40(2): 219-22.
 
68.
Sengupta T, Mohanakumar KP. 2-Phenylethylamine, a constituent of chocolate and wine, causes mitochondrial complex-I inhibition, generation of hydroxyl radicals and depletion of striatal biogenic amines leading to psycho-motor dysfunctions in Balb/c mice. Neurochem Int. 2010; 57(6): 637-46.
 
69.
Johnston JP. Some observations upon a new inhibitor of monoamine oxidase in brain tissue. Biochem Pharmacol. 1968; 17(7): 1285-97.
 
70.
Paterson IA, Juorio AV, Boulton AA. 2-Phenylethylamine: a modulator of catecholamine transmission in the mammalian central nervous system? J Neurochem. 1990; 55(6): 1827-37.
 
71.
Sabelli AC, Ciardina WJ. Amine modulation of affective behaviour. In: Sabelli AC (Ed) Chemical Modulation of Brain Function. Raven Press New York, 1973, 225-259.
 
72.
Greenshaw AJ. Functional interactions of 2-phenylethylamine and of tryptamine with brain catecholamines: implications for psychotherapeutic drug action. Prog Neuropsychopharmacol Biol Psychiatry 1989; 13(3-4): 31-43.
 
73.
Sabelli H, Fink P, Fawcett J, Tom C. Sustained antidepressant effect of PEA replacement. J Neuropsychiatry Clin Neurosci. 1996; 8(2): 168-71.
 
74.
Bunzow JR, Sonders MS, Arttamangkul S, Harrison L, Zhang G, Quigley D, et al. Amphetamine, 3,4-Methylenedioxymethamphetamine, Lysergic Acid Diethylamide, and Metabolites of the Catecholamine Neurotransmitters Are Agonists of a Rat Trace Amine Receptor. Mol. Pharmacol. 2001; 60: 1181.
 
75.
Bergman J, Yasar S, Winger G. Psychomotor stimulant effects of beta-phenylethylamine in monkeys treated with MAO-B inhibitors. Psychopharmacol (Berl) 2001; 159(1): 21-30.
 
76.
Dourish CT. A pharmacological analysis of the hyperactivity syndrome induced by beta-phenylethylamine in the mouse. Br J Pharmacol. 1982; 77(1): 129-39.
 
77.
Dourish CT, Boulton AA. The effects of acute and chronic administration of beta-phenylethylamine on food intake and body weight in rats. Prog Neuropsychopharmacol. 1981; 5(4): 411-4.
 
78.
Karila L, Petit A, Cottencin O, Reynaud M. Methamphetamine dependence: Consequences and complications. Presse Med. 2010; 39(12): 1246-53.
 
79.
Oberlender R, Nichols DE. Structural variation and (+)-amphetamine-like discriminative stimulus properties. Pharmacol Biochem Behav. 1991; 38(3): 581-6.
 
80.
Bruinvels J. Evidence for inhibition of the reuptake of 5-hydroxy-tryptamine and noradrenaline by tetrahydronaphthylamine in rat brain. Br J Pharmacol. 1971; 42(2): 281-6.
 
81.
Bruinvels J, Kemper GC. Role of noradrenaline and 5-hydroxytryptamine in tetrahydronaphthylamine-induced temperature changes in the rat. Br J Pharmacol. 1971; 43(1): 1-9.
 
82.
Dutta AK, Fei XS, Reith ME. A novel series of hybrid compounds derived by combining 2-aminotetralin and piperazine fragments: binding activity at D2 and D3 receptors. Bioorg Med Chem Lett. 2002; 12(4): 619-22.
 
83.
Mrongovius RI, Bolt AG, Hellyer RO. Comparison of the anorectic and motor activity e ects of some aminoindanes, 2-aminotetralin and amphetamine in the rat. Clin Exp Pharmacol Physiol. 1978; 5(6): 635-40.
 
84.
Holz WC, Hieble JP, Gill CA, DeMarinis RM, Pendleton RG. alpha-Adrenergic agents. 3. Behavioral effects of 2-aminotetralins. Psychopharmacology (Berl) 1982; 77(3): 259-67.
 
85.
Sharabi FM, Long JP, Rusterholz DB, Barfknecht CF. Aminotetralin analogs of methoxamine as potential hypertensive agents. Res Commun Chem Pathol Pharmacol. 1978; 19(1): 37-55.
 
86.
Moya PR, Berg KA, Gutiérrez-Hernandez MA, Sáez-Briones P, Reyes-Parada M, Cassels BK, Clarke WP. Functional Selectivity of Hallucinogenic Phenethylamine and Phenylisopropylamine Derivatives at Human 5-Hydroxytryptamine (5-HT)2A and 5-HT2C Receptors. J Pharmacol Exp Ther. 2007; 321: 1054-1061.
 
87.
Nagai F, Nonaka R, Satoh K, Kamimura H. The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain. Eur J Pharmacol. 2007; 559(2-3): 132-7.
 
88.
Beuerle G, Kovar KA, Schulze-Alexandru M. Three-dimensional quantitative structure–activity relationships of hallucinogenic phenylalkanamine and tryptamine derivatives. Studies using comparative molecular field analysis (CoMFA). Quant Struct-Act Relat. 1997; 16: 447-458.
 
89.
Maurer HH. Chemistry, pharmacology, and metabolism of emerging drugs of abuse. Ther Drug Monit. 2010; 32(5): 544-9.
 
90.
Nonaka R, Nagai F, Ogata A, Satoh K. In vitro screening of psychoactive drugs by [(35)S]GTPgammaS binding in rat brain membranes. Biol Pharm Bull. 2007; 30(12): 2328-33.
 
91.
Glennon RA, Liebowitz SM. Serotonin receptor affinity of cathinone and related analogues. J Med Chem. 1982; 25(4): 393-7.
 
92.
Theobald DS, Maurer HH. Studies on the metabolism and toxicological detection of the designer drug 4-ethyl-2,5-dimethoxy-beta-phenethylamine (2C-E) in rat urine using gas chromatographic-mass spectrometric techniques. J Chromatogr B Analyt Technol Biomed Life Sci. 2006; 842(2): 76-90.
 
93.
Theobald DS, Maurer HH. Identification of monoamine oxidase and cytochrome P450 isoenzymes involved in the deamination of phenethylamine-derived designer drugs (2C-series). Biochem Pharmacol. 2007; 73(2): 287-97.
 
94.
Kanamori T, Kuwayama K, Tsujikawa K, Miyaguchi H, Iwata YT, Inoue H, et al. In vivo metabolism of 2,5-dimethoxy-4-propylthiophenethylamine in rat. Xenobiotica 2007; 37(6): 679-92.
 
95.
Habrdova V, Peters FT, eobald DS, Maurer HH. Screening for and validated quantification of phenethylamine-type designer drugs and mescaline in human blood plasma by gas chromatography/mass spectrometry. J Mass Spectrom. 2005; 40(6): 785-95.
 
96.
Shulgin, A. Pihkal A. A chemical Love Story, Transform Press, Berkely CA, 1991.
 
97.
2-CE. http://www.erowid.org/chemical... , 2011 (access: 2012.01.23).
 
98.
Carlson, P. Minnesota teen reportedly dies from 2C-E drug overdose. 2011 http://www.imperfectparent.com... reportedly-dies-from-2c-e-drug-overdose/ (access: 2012.02.12).
 
99.
NewsOn6.com. 2011. 1 Dead, 7 Injured In Mass Drug Overdose In Konawa http://www.newson6.com/story/1... (access: 2012.02.12).
 
100.
Kjellgren A, Soussan C. Heaven and hell--a phenomenological study of recreational use of 4-HO-MET in Sweden. J Psychoactive Drugs. 2011; 43(3): 211-9.
 
101.
Fuller RW, Snoddy HD, Perry KW. Tissue distribution, metabolism and effects of bufotenine administered to rats. Neuropharmacology 1995; 34(7): 799-804.
 
102.
Cozzi NV, Gopalakrishnan A, Anderson LL, Feih JT, Shulgin AT, Daley PF, et al. Dimethyltryptamine and other hallucinogenic tryptamines exhibit substrate behavior at the serotonin uptake transporter and the vesicle monoamine transporter. J Neural Transm. 2009; 116(12): 1591-9.
 
103.
Gatch MB, Forster MJ, Janowsky A, Eshleman AJ. Abuse liability profile of three substituted tryptamines. J Pharmacol Exp Ther. 2011; 338(1): 280-9.
 
104.
Sogawa C, Sogawa N, Tagawa J, Fujino A, Ohyama K, Asanuma M, et al. 5-Methoxy-N,N-diisopropyltryptamine (Foxy), a selective and high affinity inhibitor of serotonin transporter. Toxicol Lett. 2007; 170(1): 75-82.
 
105.
Graham JH, Balster RL. Cocaine-like discriminative stimulus effects of procaine, dimethocaine and lidocaine in rats. Psychopharmacology (Berl) 1993; 110(3): 287-94.
 
106.
Rhee HM, Lee SY, Lee SM, Valentine FL. Cardiovascular effects of tropacocaine in conscious and anesthetized rabbits: lack of evidence for neuro-cardiac interactions and acute neurotoxicity. Neurotoxicology 1995; 16(1): 145-51.
 
107.
Abraham P, Pitner JB, Lewin AH, Boja JW, Kuhar MJ, Carroll FI. N-modified analogues of cocaine: synthesis and inhibition of binding to the cocaine receptor. J Med Chem. 1992; 35(1): 141-4.
 
108.
Wilcox KM, Kimmel HL, Lindsey KP, Votaw JR, Goodman MM, Howell LL. In vivo comparison of the reinforcing and dopamine transporter effects of local anesthetics in rhesus monkeys. Synapse 2005; 58(4): 220-8.
 
109.
Rigon AR, Takahashi RN. The effects of systemic procaine, lidocaine and dimethocaine on nociception in mice. Gen Pharmacol. 1996; 27(4): 647-50.
 
110.
Meyer EM, Potter LT, De Vane CL, Irwin I, MacKay SL, Miller R, et al. Effects of benzoyltropine and tropacocaine on several cholinergic processes in the rat brain. J Pharmacol Exp Ther. 1990; 254: 584.
 
111.
Jones RT. The pharmacology of cocaine. NIDA Res Monogr. 1984; 50: 34-53.
 
112.
Bosy TZ, Ruth JA. Differential inhibition of synaptosomal accumulation of [3H]-monoamines by cocaine, tropacocaine and amphetamine in four inbred strains of mice. Pharmacol Biochem Behav. 1989; 34(1): 165-72.
 
113.
Gatley SJ. Activities of the enantiomers of cocaine and some related compounds as substrates and inhibitors of plasma butyryl-cholinesterase. Biochem Pharmacol. 1991; 41(8): 1249-54.
 
114.
Fairbanks DN, Fairbanks GR. Cocaine uses and abuses. Ann Plast Surg. 1983; 10(6): 452-7.
 
115.
Wesson DR, Smith DE. Cocaine: its use for central nervous system stimulation including recreational and medical uses. NIDA Res Monogr. 1977; 13: 137-52.
 
116.
Fischman MW. The behavioral pharmacology of cocaine in humans. NIDA Res Monogr. 1984; 50: 72-91.
 
117.
Washton AM, Tatarsky A. Adverse effects of cocaine abuse. NIDA Res Monogr. 1984; 49: 247-54.
 
118.
Schindler CW, Tella SR, Erzouki HK, Goldberg SR. Pharmacological mechanisms in cocaine’s cardiovascular effects. Drug Alcohol Depend. 1995; 37(3): 183-91.
 
119.
The European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) Synthetic cocaine derivatives, 2011. http://www.emcdda.europa.eu/pu... les/synthetic-cocaine-derivatives (access: 2012.03.06).
 
120.
Drugnet Ireland, 2010. Alcohol and Drug Research Newsletter; Fluorotropacocaine p15. http://www.hrb.ie/uploads/tx_h... (access: 2012.02.24).
 
121.
Kavanagh P, Angelov D, O’Brien J, Fox J, O’Donnell C, Christie R, et al. The syntheses and characterization 3?-(4-fluorobenzoyloxy)tropane (fluorotropacocaine) and its 3? isomer. Drug Test Anal. 2012; 4(1): 33-8.
 
122.
Wohlfarth A, Weinmann W. Bioanalysis of new designer drugs. Bioanalysis 2010; 2(5): 965-79.
 
123.
Du C, Yu M, Volkow ND, Koretsky AP, Fowler JS, Benveniste H. Cocaine Increases the Intracellular Calcium Concentration in Brain Independently of Its Cerebrovascular Effects. J Neurosci. 2006; 26: 11522-11531.
 
124.
Bill TJ, Clayman MA, Morgan RF, Gampper TJ. Lidocaine Metabolism Pathophysiology, Drug Interactions, and Surgical Implications. Aesthet Surg J. 2004; 24(4): 307-11.
 
125.
Zeida A, Baraka A. Is euphoria a side-effect of lidocaine? Anaesthesia 2004; 59(12): 1253-4.
 
126.
Blanke J, Wolstein J, Paulus HJ. Euphoric effect of lidocaine. Psychiatrische Praxis 1996; 23: 90–1.
 
127.
Turner WM. Lidocaine and psychotic reactions. Ann Intern Med. 1982; 97(1): 149-50.
 
128.
Saravay SM, Marke J, Steinberg MD, Rabiner CJ. ‘Doom anxiety’ and delirium in lidocaine toxicity. Am J Psychiatry. 1987; 144(2): 159-63.
 
129.
Voigt L. Anaesthetic management of the cocaine abuse patient. AANA J. 1995; 63(5): 438-43.
 
130.
Gold MS, Reichling DB, Hampl KF, Drasner K, Levine JD. Lidocaine Toxicity in Primary Afterent Neurons from the Rat1. J Pharmacol Exp Ther. 1998; 285: 413-421.
 
131.
Sakura S, Kirihara Y, Muguruma T, Kishimoto T, Saito Y. The Comparative Neurotoxicity of Intrathecal Lidocaine and Bupivacaine in Rats. Anesth. Analg. 2005; 101: 541-547.
 
132.
Haller I, Hausott B, Tomaselli B, Keller C, Klimaschewski L, Gerner P, et al. Neurotoxicity of lidocaine involves specific activation of the p38 mitogen-activated protein kinase, but not extracellular signal-regulated or c-jun N-terminal kinases, and is mediated by arachidonic acid metabolites. Anesthesiology 2006; 105(5): 1024-33.
 
133.
Lirk P, Haller I, Colvin HP, Lang L, Tomaselli B, Klimaschewski L, et al. In Vitro, Inhibition of Mitogen-Activated Protein Kinase Pathways Protects Against Bupivacaine- and Ropivacaine-Induced Neurotoxicity. Anesth Analg. 2008; 106: 1456-1464.
 
134.
Sedefov R, Gallegos A. 2010. Assessment of the functioning of the Council Decision on information exchange, risk assessment and control of new psychoactive substances. 33 rd Meeting of the EMCDDA. att_ 121621_EN_Annex 4_Assessment of the risk assessment procedure (RS) www@emcdda.europa.eu. (access: 2012.01.30).
 
135.
Haarder B, Petersen L. Bekendtgørelse om ændring af bekendtgørelseom euforiserende stoffer. 2011. https://www.retsinformation.dk... (access: 2012.01.03).
 
136.
Nichols DE, Johnson MP, Oberlender R. 5-Iodo-2-aminoindan, a nonneurotoxic analogue of p-iodoamphetamine. Pharmacol Biochem Behav. 1991; 38(1): 135-9.
 
137.
Rudnick G, Wall SC. Non-neurotoxic amphetamine derivatives release serotonin through serotonin transporters. Mol Pharmacol. 1993; 43: 271.
 
138.
Sainsbury PD, Kicman AT, Archer RP, King LA, Braithwaite RA. Aminoindanes – the next wave of ‘legal highs’? Drug Test Anal. 2011; 3(7-8): 479-82.
 
139.
Long J. Update on psychoactive substances sold in head shops and on line. Drugnet Ireland. 2010; 34: 15-18.
 
140.
Bolton D, Boyfield I, Coldwell MC, Hadley MS, Healy MAM, Johnson CN, et al. Novel 2,5-disubstituted-1H-pyrroles with high affinity for the dopamine D3 receptor. Chem Inform. 1996; 27: no. doi: 10.1002/chin.199642123.
 
141.
Rodrıguez LJ, Medina Y, Suarez-Roca H, Migliore de Angel B, Israel A, et al. Conformational theoretical study of substituted and non-substituted N-aralkyl-2-aminoindans and its relation with dopaminergic activity. J Mol Struct. (Theochem) 2003; 636: 1-8.
 
142.
Arneria SP, Maixner W, Long JP, Mott J, Barfknecht CF, Perez JA, et al. Structure-activity relationships of 2-aminotetralins and 2-aminoindanes: inhibitory neuroeffector mechanisms in isolated guinea-pigilea. Arch Int Pharmacodyn Ther. 1982; 258(1): 84-99.
 
143.
Witkin LB, Heubner CF, Galdi F, O’Keefe E, Spitaletta P, Plummer AJ. Pharmacology of 2-amino-indane hydrochloride (SU-8629): a potent ono-narcotic analgesic. J Pharmacol Exp Ther. 1961; 133: 400-408.
 
144.
Fuller RW, Baker JC, Molloy BB. Biological disposition of rigid analogs of amphetamine. J Pharm Sci. 1977; 66(2): 271-2.
 
145.
Johnson MP, Nichols DE. Combined administration of a non-neurotoxic 3,4-methylenedioxymethamphetamine analogue with amphetamine produces serotonin neurotoxicity in rats. Neuropharmacol. 1991; 30(7): 819-822.
 
146.
Li Q, Murakami I, Stall S, Levy AD, Brownfield MS, Nichols DE, et al. Neuroendocrine pharmacology of three serotonin releasers: 1-(1,3- benzodioxol-5-yl)-2-(methylamino)butane (MBDB), 5-methoxy-6-methyl-2- aminoindan (MMAi) and p-methylthioamphetamine (MTA). J Pharmacol Ex Ther. 1996; 279: 1261.
 
147.
Graham JM, Coughenour LL, Barr BM, Rock DL, Nikam SS. 1-Aminoindanes as novel motif with potential atypical antipsychotic properties. Bioorg Med Chem Lett. 2008; 18(2): 489-93.
 
148.
Oldfield V, Keating GM, Perry CM. Rasagiline: a review of its use in the management of Parkinson’s disease. Drugs 2007; 67(12): 1725-47.
 
149.
Gee P, Jackson S, Easton J. Another bitter pill: a case of toxicity from DMAA party pills. N Z Med J. 2010; 123(1327): 124-7.
 
150.
Maj J. Effect of memantine on central neurotransmitter systems. Review of the results. Arzneimittelforschung 1982; 32(10): 1256-9.
 
151.
Marsh DF, Howard A, Herring DA. The comparative pharmacology of the isomeric nitrogen methyl substituted hepatylamines. J Pharmacol Exp er. 1951; 103: 325-329.
 
152.
Bloomer RJ, Harvey IC, Farney TM, Bell ZW, Canale RE. Effects of 1,3-dimethylamylamine and caffeine alone or in combination on heart rate and blood pressure in healthy men and women. Phys Sportsmed. 2011; 39(3): 111-20.
 
153.
NIH Office of Dietary Supplements; Newsletter, 2012. Dietary Supplements Removed From Military Facilities for Health Concerns. http://ods.od.nih.gov/News/ e_Scoop_-_March_2012.aspx and http://hprc-online.org/blog/dm... (access: 2012.03.18).
 
154.
Steward I. Party pill inventor backs restriction. 2009. http://www.stuff.co.nz/the-pre... (access: 2012.02.06).
 
155.
Lisi A, Hasick N, Kazlauskas R, Goebel C. Studies of methylhexaneamine in supplements and geranium oil. Drug Test Anal. 2011; 3(11-12): 873-6.
 
156.
The World Anti-Doping Code. THE 2012 PROHIBITED LIST INTERNATIONAL STANDARD; 2012. http://www.wada-ama.org/Docume... (access: 2012.03.23).
 
157.
Perrenoud L, Saugy M, Saudan C. Detection in urine of 4-methyl-2-hexaneamine, a doping agent. J Chromatogr B Analyt Technol Biomed Life Sci. 2009; 877(29): 3767-70.
 
158.
Chao JM, Der Marderosian AH. Ergoline alkaloidal constituents of Hawaiian baby wood rose, Argyreia nervosa (Burm. f.) Bojer. J Pharm Sci. 1973; 62(4): 588-91.
 
159.
Borsutzky M, Passie T, Paetzold W, Emrich HM, Schneider U. Hawaiian baby woodrose: (Psycho-) Pharmacological effects of the seeds of Argyreia nervosa. A case-orientated demonstration. Nervenarzt 2002; 73(9): 892-6.
 
160.
Gopel C, Maras A, Schmidt MH. Hawaiian baby rose wood: case report of an argyreia nervosa induced toxic psychosis. Psychiatr Prax. 2003; 30(4): 223-4.
 
161.
Kremer C, Paulke A, Wunder C, Toennes SW. Variable adverse effects in subjects after ingestion of equal doses of Argyreia nervosa seeds. Forensic Sci Int. 2012; 214(1-3): e6-8.
 
162.
Schmidt MM, Sharma A, Schifano F, Feinmann C. “Legal highs” on the net-Evaluation of UK-based Websites, products and product information. Forensic Sci Int. 2011; 206(1-3): 92-7.
 
163.
Sheffler DJ, Roth BL. Salvinorin A: the “magic mint” hallucinogen finds a molecular target in the kappa opioid receptor. Trends Pharmacol Sci. 2003; 24(3): 107-9.
 
164.
Yan F, Roth BL. Salvinorin A: a novel and highly selective kappa-opioid receptor agonist. Life Sci. 2004; 75(22): 2615-9.
 
165.
Kelly BC. Legally tripping: a qualitative pro le of Salvia divinorum use among young adults. J Psychoactive Drugs 2011; 43(1): 46-54.
 
166.
Roth BL, Baner K, Westkaemper R, Siebert D, Rice KC Steinberg S, et al. Salvinorin A: A potent naturally occurring nonnitrogenous opioid selective agonist. PNAS 2002; 99: 11934-11939.
 
167.
Baggott MJ, Erowid E, Erowid F, Galloway GP, Mendelson J. Use patterns and self-reported effects of Salvia divinorum: an internet-based survey. Drug Alcohol Depend. 2010; 111(3): 250-6.
 
168.
Johnson MW, MacLean KA, Reissig CJ, Prisinzano TE, Griffiths RR. Human psychopharmacology and dose-effects of salvinorin A, a kappa opioid agonist hallucinogen present in the plant Salvia divinorum. Drug Alcohol Depend. 2011; 115(1-2): 150-5.
 
169.
Prisinzano TE. Psychopharmacology of the hallucinogenic sage Salvia divinorum. Life Sci. 2005; 78(5): 527-31.
 
170.
Grundmann O, Phipps SM, Zadezensky I, Butterweck V. Salvia divinorum and salvinorin A: an update on pharmacology and analytical methodology. Planta Med. 2007; 73(10): 1039-46.
 
171.
Braida D, Donzelli A, Martucci R, Capurro V, Sala M. Learning and Memory Impairment Induced by Salvinorin A, the Principal Ingredient of Salvia divinorum, in Wistar Rats. Int J Toxicol. 2011; 30: 650-661.
 
172.
Vohra R, Seefeld A, Cantrell FL, Clark RF. Salvia divinorum: exposures reported to a statewide poison control system over 10 years. J Emerg Med. 2011; 40(6): 643-50.
 
173.
Bucheler R, Gleiter CH, Schwoerer P, Gaertner I. Use of nonprohibited hallucinogenic plants: increasing relevance for public health? A case report and literature review on the consumption of Salvia divinorum (Diviner’s Sage). Pharmacopsychiatry 2005; 38(1): 1-5.
 
174.
Wu LT, Woody GE, Yang C, Li JH, Blazer DG. Recent national trends in Salvia divinorum use and substance-use disorders among recent and former Salvia divinorum users compared with nonusers. Subst Abuse Rehabil. 2011; (2): 53-68.
 
175.
Casselman I, Heinrich M. Novel use patterns of Salvia divinorum: unobtrusive observation using YouTube? J Ethnopharmacol. 2011; 138(3): 662-7.
 
176.
Lange JE, Daniel J, Homer K, Reed MB, Clapp JD. Salvia divinorum: effects and use among YouTube users. Drug Alcohol Depend. 2010; 108(1-2): 138-40.
 
177.
Hanes KR. Antidepressant effects of the herb Salvia divinorum: a case report. J Clin Psychopharmacol. 2001; 21(6): 634-5.
 
178.
Ahern NR, Greenberg CS. Psychoactive herb use and youth: a closer look at salvia divinorum. J Psychosoc Nurs Ment Health Serv. 2011; 49(8): 16-9.
 
179.
Bosch OG, Quednow BB, Seifritz E, Wetter TC. Reconsidering GHB: orphan drug or new model antidepressant? J Psychopharmacol. 2012; 26(5): 618-28.
 
180.
Sewell RA, Petrakis IL. Does Gamma-Hydroxybutyrate (GHB) Have a Role in the Treatment of Alcoholism? Alcohol. 2011; 46: 1-2.
 
181.
Karila L, Reynaud M. GHB and synthetic cathinones: clinical effects and potential consequences. Drug Test Anal. 2011; 3(9): 552-9.
 
182.
Kashyap GL, Patel AG. Unusual presentation of a patient with GBL withdrawal: a case report. Psychiatr Danub. 2011, 23 Suppl 1: S32-4.
 
183.
Galicia M, Nogue S, Miró O. Liquid ecstasy intoxication: clinical features of 505 consecutive emergency department patients. Emerg Med J. 2011; 28: 462-466.
 
184.
Brailsford AD, Cowan DA, Kicman AT. Pharmacokinetic Properties of -Hydroxybutyrate (GHB) in Whole Blood, Serum, and Urine. J Anal Toxicol. 2012; 36: 88-95.
 
185.
Németh Z, Kun B, Demetrovics Z. Review: The involvement of gamma-hydroxybutyrate in reported sexual assaults: a systematic review. J Psychopharmacol. 2010; 24: 1281-1287.
 
186.
Nastolatki rezygnują z dopalaczy. Teraz trują się płynami do higieny intymnej i czyszczenia metali. Kraków.NaszeMiasto.pl, 2012. http://natablicy.pl/przerwa/na... (access: 2012.03.26).
 
187.
Travis A. ‘Legal highs’ should be automatically banned, says government drugs adviser. Advisory council calls for tougher US-style system to control designer drugs that mimic effects of illegal substances. 2011, http://www.guardian.co.uk/soci... (access: 2012.01.14).
 
188.
Rinaldi-Carmona M, Calandra B, Shire D, Bouaboula M, Oustric D, Barth F, et al. Characterization of two cloned human CB1 cannabinoid receptor isoforms. J Pharmacol Exp Ther. 1996; 278(2): 871-8.
 
189.
Satoh K, Nonaka R. In-vitro screening of psychoactive drugs to prevent abuses. Yakugaku Zasshi 2008; 128(12): 1771-82.
 
190.
United Nations Office on Drugs and Crime (UNODC). Annual Report. 2010, http://www.unodc.org/unodc/en/.... (access: 2012.01.16).
 
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