Desoxypipradrol, also known as 2-⁠diphenylmethylpiperidine (2-DPMP), is a drug developed by Ciba in the 1950s which acts as a norepinephrine-dopamine reuptake inhibitor (NDRI).

Chemistry

Desoxypipradrol is closely related on a

structural A structure is an arrangement and organization of interrelated elements in a material object or system, or the object or system so organized. Material structures include man-made objects such as buildings and machines and natural objects such ...

level to the compounds

methylphenidate Methylphenidate, sold under the brand names Ritalin and Concerta among others, is the most widely prescribed central nervous system (CNS) stimulant medication used to treat attention deficit hyperactivity disorder (ADHD) and, to a lesser extent, ...

and

pipradrol Pipradrol (Meratran) is a mild central nervous system stimulant ( norepinephrine-dopamine reuptake inhibitor) that is no longer widely used in most countries due to concerns about its abuse potential. Pipradrol is still used in some European cou ...

, all three of which share a similar

pharmacological Pharmacology is a branch of medicine, biology and pharmaceutical sciences concerned with drug or medication action, where a drug may be defined as any artificial, natural, or endogenous (from within the body) molecule which exerts a biochemica ...

action Action may refer to: * Action (narrative), a literary mode * Action fiction, a type of genre fiction * Action game, a genre of video game Film * Action film, a genre of film * ''Action'' (1921 film), a film by John Ford * ''Action'' (1980 fil ...

. Of these three

piperidine Piperidine is an organic compound with the molecular formula (CH2)5NH. This heterocyclic compound, heterocyclic amine consists of a six-membered ring containing five methylene bridges (–CH2–) and one amine bridge (–NH–). It is a colorless ...

s, desoxypipradrol has the longest elimination

half-life Half-life (symbol ) is the time required for a quantity (of substance) to reduce to half of its initial value. The term is commonly used in nuclear physics to describe how quickly unstable atoms undergo radioactive decay or how long stable ato ...

, as it is a highly

lipophilic Lipophilicity (from Greek λίπος "fat" and φίλος "friendly"), refers to the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. Such non-polar solvents are themselves lipop ...

molecule A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bioch ...

lacking

polar Polar may refer to: Geography Polar may refer to: * Geographical pole, either of two fixed points on the surface of a rotating body or planet, at 90 degrees from the equator, based on the axis around which a body rotates * Polar climate, the c ...

functional group In organic chemistry, a functional group is a substituent or moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions regardless of the rest ...

s that are typically targeted by

metabolic Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

s, giving it an extremely long duration of action when compared to most psychostimulants. Methylphenidate, on the other hand, is a short-acting compound, as it possesses a

methyl In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula . In formulas, the group is often abbreviated as Me. This hydrocarbon group occurs in many ...

ester In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ar ...

moiety Moiety may refer to: Chemistry * Moiety (chemistry), a part or functional group of a molecule ** Moiety conservation, conservation of a subgroup in a chemical species Anthropology * Moiety (kinship), either of two groups into which a society is ...

that is easily cleaved, forming a highly polar

acid In computer science, ACID ( atomicity, consistency, isolation, durability) is a set of properties of database transactions intended to guarantee data validity despite errors, power failures, and other mishaps. In the context of databases, a sequ ...

group, while pipradrol is intermediate in duration, possessing a

hydroxyl In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydroxy ...

group which can be conjugated (e.g. with

glucuronide A glucuronide, also known as glucuronoside, is any substance produced by linking glucuronic acid to another substance via a glycosidic bond. The glucuronides belong to the glycosides. Glucuronidation, the conversion of chemical compounds to glucur ...

) to increase its

hydrophilicity A hydrophile is a molecule or other molecular entity that is attracted to water molecules and tends to be dissolved by water.Liddell, H.G. & Scott, R. (1940). ''A Greek-English Lexicon'' Oxford: Clarendon Press. In contrast, hydrophobes are no ...

and facilitate

excretion Excretion is a process in which metabolic waste is eliminated from an organism. In vertebrates this is primarily carried out by the lungs, kidneys, and skin. This is in contrast with secretion, where the substance may have specific tasks after lea ...

, but no easily metabolized groups.

History

Desoxypipradrol was developed by the pharmaceutical company CIBA (now called

Novartis Novartis AG is a Swiss-American multinational pharmaceutical corporation based in Basel, Switzerland and Cambridge, Massachusetts, United States (global research).name="novartis.com">https://www.novartis.com/research-development/research-loc ...

) in the 1950s, and researched for applications such as the treatment of

narcolepsy Narcolepsy is a long-term neurological disorder that involves a decreased ability to regulate sleep–wake cycles. Symptoms often include periods of excessive daytime sleepiness and brief involuntary sleep episodes. About 70% of those affec ...

and

ADHD Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by excessive amounts of inattention, hyperactivity, and impulsivity that are pervasive, impairing in multiple contexts, and otherwise age-inapp ...

; however, it was dropped from development after the related drug methylphenidate was developed by the same company. Methylphenidate was felt to be the superior drug for treating ADHD due to its shorter duration of action and more predictable

pharmacokinetics Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to determining the fate of substances administered ...

, and while desoxypipradrol was researched for other applications (such as facilitation of rapid recovery from

anaesthesia Anesthesia is a state of controlled, temporary loss of sensation or awareness that is induced for medical or veterinary purposes. It may include some or all of analgesia (relief from or prevention of pain), paralysis (muscle relaxation), am ...

), its development was not continued. The hydroxylated derivative

was, however, introduced as a clinical drug indicated for depression,

and cognitive enhancement in organic

dementia Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affe ...

Detection in biological specimens

Desoxypipradrol may be quantitated in

blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the c ...

plasma Plasma or plasm may refer to: Science * Plasma (physics), one of the four fundamental states of matter * Plasma (mineral), a green translucent silica mineral * Quark–gluon plasma, a state of matter in quantum chromodynamics Biology * Blood pla ...

urine Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excretion, excreted from the body through the urethra. Cel ...

by liquid chromatography-mass spectrometry to confirm a diagnosis of poisoning in hospitalized patients or to provide evidence in a medicolegal death investigation. Blood or plasma desoxypipradrol concentrations are expected to be in a range of 10–50 μg/L in persons using the drug recreationally, >100 μg/L in intoxicated patients and >600 μg/L in victims of acute overdosage.

Legal status

Desoxypipradrol's structural similarity to

makes it possible that it would be considered a controlled substance analogue in several countries such as

Australia Australia, officially the Commonwealth of Australia, is a Sovereign state, sovereign country comprising the mainland of the Australia (continent), Australian continent, the island of Tasmania, and numerous List of islands of Australia, sma ...

and

New Zealand New Zealand ( mi, Aotearoa ) is an island country in the southwestern Pacific Ocean. It consists of two main landmasses—the North Island () and the South Island ()—and over 700 smaller islands. It is the sixth-largest island count ...

China

As of October 2015 2-DPMP is a controlled substance in China.

United Kingdom

As of 4 November 2010, the UK Home Office announced a ban on the importation of 2-DPMP, following a recommendation from the

ACMD The Advisory Council on the Misuse of Drugs (ACMD) is a British statutory non-departmental public body, advisory non-departmental public body, which was established under the Misuse of Drugs Act 1971. Mandate Its terms of reference, according to ...

. Prior to the import ban, desoxypipradrol was sold as a 'legal high' in several products, most notably "Ivory wave". Its use lead to several

Emergency Department An emergency department (ED), also known as an accident and emergency department (A&E), emergency room (ER), emergency ward (EW) or casualty department, is a medical treatment facility specializing in emergency medicine, the acute care of pati ...

visits which prompted the

UK government ga, Rialtas a Shoilse gd, Riaghaltas a Mhòrachd , image = HM Government logo.svg , image_size = 220px , image2 = Royal Coat of Arms of the United Kingdom (HM Government).svg , image_size2 = 180px , caption = Royal Arms , date_es ...

to commission a review from the

. One man had ingested nearly 1 gram of the drug which may have been fatal without sedation with an anaesthetic dose of a benzodiazepine administered in accident and emergency. The Advisory Council on the Misuse of Drugs stated in their report that: :"''there are serious harms associated with 2-DPMP... typically prolonged agitation (lasting up to 5 days after drug use which is sometimes severe, requiring physical restraint), paranoia, hallucinations and myoclonus (muscle spasms/twitches).''" 2-DPMP was due to become a class B drug on 28 March 2012, but the bill was scrapped as two steroids deemed not to be abusable were included in the bill but were later recommended to remain uncontrolled. There was a new discussion about its fate on April 23, 2012, where it was decided that the bill would be rewritten and 2-DPMP would still be banned. It was also decided that the bill would be a blanket ban of related chemicals. Desoxypipradrol was eventually made a class B drug and placed in Schedule I on 13 June 2012. There were no recorded deaths from the drug between the banning of its import and the banning of its possession. "Esters and ethers of pipradrol" were controlled with the same amendment as class C drugs.

References

{{Monoamine reuptake inhibitors Norepinephrine–dopamine reuptake inhibitors Stimulants 2-Piperidinyl compounds Designer drugs Benzhydryl compounds