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Abstract
Introduction. Over the last decade there has been greater use of novel psychoactive substances (‘legal highs’) across Europe and the United States, including increasing reports of use of diphenylprolinol (D2PM) and desoxypipradrol (2-DPMP). This review will discuss the pharmacology and mechanisms of action of these two compounds, available data on their sources and prevalence of use and reports of acute toxicity and fatalities associated with their use. Methods. PubMed was searched using the search terms ‘D2PM’, ‘2-DPMP’, ‘diphenyl-2-pyrrolidinyl-methanol’, ‘diphenylprolinol’, ‘2-diphenylmethylpiperidine’ and ‘desoxypipradrol’. These searches identified 70 articles, only five of which were relevant. Pharmacology and mechanisms of action. D2PM is a pyrrolidine analogue and 2-DPMP is a desoxy analogue of pipradrol. Animal studies have shown that 2-DPMP increases the release of dopamine and decreases dopamine re-uptake comparable to the effects of cocaine. The binding and activity of D2PM at the dopamine re-uptake transporter, based on currently published data, is also similar to cocaine, although it appears that D2PM has less biological activity. Sources and prevalence of use. D2PM and 2-DPMP is available from internet-based suppliers and street level drug dealers; there is currently no systematic data to be able to determine the relative importance of these routes of supply. There is no population level, and limited subpopulation level, data on the prevalence of use of D2PM/2-DPMP. In one 2011 study, 1.6% of 315 individuals in ‘gay friendly’ nightclubs in South London reported that they had used a pipradrol: 1.0% had used within the last year and 0.6% had used or were planning to use a pipradrol on the night of the survey. Acute toxicity. Reports on internet discussion fora describe prolonged euphoria and stimulant effects including euphoria, sweating and bruxism with use of D2PM and 2-DPMP. The first report of analytically confirmed acute D2PM toxicity described chest pain and sympathomimetic features (hypertension and tachycardia). Five individuals with analytically confirmed acute D2PM toxicity developed agitation/anxiety and/or insomnia lasting 24–96 h in addition to sympathomimetic features (palpitations, anxiety and agitation). Reports of 49 enquiries relating to a ‘legal high’ product called ‘Whack’ (which on analysis was found to contain 2-DPMP and fluorotropacocaine) commonly described unwanted cardiovascular (hypertension in 10/49 and tachycardia in 12/49) and neuropsychiatric (agitation in 14/49 and psychosis in 13/49) effects; the neuropsychiatric effects were prolonged, and persisted for up to 5 days. No analysis of biological samples was undertaken so it is not possible to determine which of these agents if any was responsible for the clinical features. In a series of 26 cases related to the use of ‘Ivory Wave’ (analysis of a similar ‘Ivory Wave’ product showed that it contained 2-DPMP), 96% had neuropsychiatric features. Cases presented up to 1 week after use with tachycardia, dystonia, rhabdomyolysis, agitation, hallucinations and paranoia. Confirmatory biological sample analysis was either not available (85.3% of cases) or negative (2.9% of cases) for 2-DPMP; it was positive for 2-DPMP in four (11.8%) of the cases (80% of those where biological analysis was undertaken). D2PM and 2-DPMP related fatalities. Although 2-DPMP has been detected in three fatalities, its role in these deaths has not yet been established. There have been no reports of deaths directly attributed to either D2PM or 2-DPMP. Conclusions. There is emerging evidence of the use of D2PM and 2-DPMP in Europe. D2PM and 2-DPMP have sympathomimetic properties similar to cocaine and, in addition, prolonged and clinically significant neuropsychiatric symptoms have been reported.