Desoxypipradrol
Encyclopedia
Desoxypipradrol, also known as 2-diphenylmethylpiperidine (2-DPMP), acts as a norepinephrine-dopamine reuptake inhibitor
(NDRI) developed by Ciba in the 1950s
Desoxypipradrol is closely related on a structural
level to the compounds methylphenidate
and pipradrol
, all three of which share a similar pharmacological action
. Of these three piperidine
s, desoxypipradrol has the longest elimination half-life
, as it is a highly lipophilic
molecule
lacking polar
functional group
s that are typically targeted by metabolic enzyme
s. Methylphenidate, on the other hand, is a short-acting compound, as it possesses a methyl-ester
moiety that is easily cleaved, forming a highly polar acid
group, while pipradrol is intermediate in duration, possessing a hydroxyl
group which can be conjugated (e.g. with glucuronide
) to increase its hydrophilicity and facilitate excretion
, but no easily metabolized groups.
Desoxypipradrol was developed by the pharmaceutical company CIBA (now called Novartis
) in the 1950s, and researched for applications such as the treatment of narcolepsy
and ADHD; 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
, and while desoxypipradrol was researched for other applications (such as facilitation of rapid recovery from anaesthesia), its development was not continued. The hydroxylated derivative pipradrol
was, however, introduced as a clinical drug indicated for depression, narcolepsy
and cognitive enhancement in organic dementia
.
Desoxypipradrol might prove quite useful for its original application of treating attention-deficit hyperactivity disorder
(ADHD) and depression, considering that the short half-life of common medications such as methylphenidate and dextroamphetamine
has led to the development of long-acting, delayed-release formulations of these drugs. Some individuals with ADHD prefer long-acting stimulant formulations, which allow for once-daily dosing.
Desoxypipradrol is not specifically listed as a controlled drug in any country at the present time, but its structural similarity to pipradrol
makes it possible that it would be considered a controlled substance analogue
in several countries such as Australia
and New Zealand
. As of the 4th November 2010, the UK Home Office
announced a ban on the importation of 2-DPMP, following a recommendation from the ACMD.
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
visits which prompted the UK government to commission a review from the ACMD One man had ingested nearly 1 gram of the drug and this would 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:
Norepinephrine-dopamine reuptake inhibitor
A norepinephrine-dopamine reuptake inhibitor is a drug which acts as a reuptake inhibitor for the neurotransmitters norepinephrine and dopamine by blocking the action of the norepinephrine transporter and the dopamine transporter , respectively...
(NDRI) developed by Ciba in the 1950s
Desoxypipradrol is closely related on a structural
Chemical structure
A chemical structure includes molecular geometry, electronic structure and crystal structure of molecules. Molecular geometry refers to the spatial arrangement of atoms in a molecule and the chemical bonds that hold the atoms together. Molecular geometry can range from the very simple, such as...
level to the compounds methylphenidate
Methylphenidate
Methylphenidate is a psychostimulant drug approved for treatment of attention-deficit hyperactivity disorder, postural orthostatic tachycardia syndrome and narcolepsy. It may also be prescribed for off-label use in treatment-resistant cases of lethargy, depression, neural insult and obesity...
and pipradrol
Pipradrol
Pipradrol is a mild central nervous system stimulant that is no longer widely used in most countries due to concerns about its abuse potential, although this is less of a problem than with other stimulants that still are in current use such as methylphenidate...
, all three of which share a similar pharmacological action
Mechanism of action
In pharmacology, the term mechanism of action refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect...
. Of these three piperidine
Piperidine
Piperidine is an organic compound with the molecular formula 5NH. This heterocyclic amine consists of a six-membered ring containing five methylene units and one nitrogen atom...
s, desoxypipradrol has the longest elimination half-life
Half-life
Half-life, abbreviated t½, is the period of time it takes for the amount of a substance undergoing decay to decrease by half. The name was originally used to describe a characteristic of unstable atoms , but it may apply to any quantity which follows a set-rate decay.The original term, dating to...
, as it is a highly lipophilic
Lipophilic
Lipophilicity, , refers to the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. These non-polar solvents are themselves lipophilic — the axiom that like dissolves like generally holds true...
molecule
Molecule
A molecule is an electrically neutral group of at least two atoms held together by covalent chemical bonds. Molecules are distinguished from ions by their electrical charge...
lacking polar
Chemical polarity
In chemistry, polarity refers to a separation of electric charge leading to a molecule or its chemical groups having an electric dipole or multipole moment. Polar molecules interact through dipole–dipole intermolecular forces and hydrogen bonds. Molecular polarity is dependent on the difference in...
functional group
Functional group
In organic chemistry, functional groups are specific groups of atoms within molecules that are responsible for the characteristic chemical reactions of those molecules. The same functional group will undergo the same or similar chemical reaction regardless of the size of the molecule it is a part of...
s that are typically targeted by metabolic enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s. Methylphenidate, on the other hand, is a short-acting compound, as it possesses a methyl-ester
Ester
Esters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH group is replaced by an -O-alkyl group, and most commonly from carboxylic acids and...
moiety that is easily cleaved, forming a highly polar acid
Acid
An acid is a substance which reacts with a base. Commonly, acids can be identified as tasting sour, reacting with metals such as calcium, and bases like sodium carbonate. Aqueous acids have a pH of less than 7, where an acid of lower pH is typically stronger, and turn blue litmus paper red...
group, while pipradrol is intermediate in duration, possessing a hydroxyl
Hydroxyl
A hydroxyl is a chemical group containing an oxygen atom covalently bonded with a hydrogen atom. In inorganic chemistry, the hydroxyl group is known as the hydroxide ion, and scientists and reference works generally use these different terms though they refer to the same chemical structure in...
group which can be conjugated (e.g. with glucuronide
Glucuronide
A glucuronide, also known as glucuronoside, is any substance produced by linking glucuronic acid to another substance via a glycosidic bond...
) to increase its hydrophilicity and facilitate excretion
Excretion
Excretion is the process by which waste products of metabolism and other non-useful materials are eliminated from an organism. 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 leaving the cell...
, but no easily metabolized groups.
Desoxypipradrol was developed by the pharmaceutical company CIBA (now called Novartis
Novartis
Novartis International AG is a multinational pharmaceutical company based in Basel, Switzerland, ranking number three in sales among the world-wide industry...
) in the 1950s, and researched for applications such as the treatment of narcolepsy
Narcolepsy
Narcolepsy is a chronic sleep disorder, or dyssomnia, characterized by excessive sleepiness and sleep attacks at inappropriate times, such as while at work. People with narcolepsy often experience disturbed nocturnal sleep and an abnormal daytime sleep pattern, which often is confused with insomnia...
and ADHD; 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
Pharmacokinetics, sometimes abbreviated as PK, is a branch of pharmacology dedicated to the determination of the fate of substances administered externally to a living organism...
, and while desoxypipradrol was researched for other applications (such as facilitation of rapid recovery from anaesthesia), its development was not continued. The hydroxylated derivative pipradrol
Pipradrol
Pipradrol is a mild central nervous system stimulant that is no longer widely used in most countries due to concerns about its abuse potential, although this is less of a problem than with other stimulants that still are in current use such as methylphenidate...
was, however, introduced as a clinical drug indicated for depression, narcolepsy
Narcolepsy
Narcolepsy is a chronic sleep disorder, or dyssomnia, characterized by excessive sleepiness and sleep attacks at inappropriate times, such as while at work. People with narcolepsy often experience disturbed nocturnal sleep and an abnormal daytime sleep pattern, which often is confused with insomnia...
and cognitive enhancement in organic dementia
Dementia
Dementia is a serious loss of cognitive ability in a previously unimpaired person, beyond what might be expected from normal aging...
.
Desoxypipradrol might prove quite useful for its original application of treating attention-deficit hyperactivity disorder
Attention-deficit hyperactivity disorder
Attention deficit hyperactivity disorder is a developmental disorder. It is primarily characterized by "the co-existence of attentional problems and hyperactivity, with each behavior occurring infrequently alone" and symptoms starting before seven years of age.ADHD is the most commonly studied and...
(ADHD) and depression, considering that the short half-life of common medications such as methylphenidate and dextroamphetamine
Dextroamphetamine
Dextroamphetamine is a psychostimulant drug which is known to produce increased wakefulness and focus as well as decreased fatigue and decreased appetite....
has led to the development of long-acting, delayed-release formulations of these drugs. Some individuals with ADHD prefer long-acting stimulant formulations, which allow for once-daily dosing.
Desoxypipradrol is not specifically listed as a controlled drug in any country at the present time, but its structural similarity to pipradrol
Pipradrol
Pipradrol is a mild central nervous system stimulant that is no longer widely used in most countries due to concerns about its abuse potential, although this is less of a problem than with other stimulants that still are in current use such as methylphenidate...
makes it possible that it would be considered a controlled substance analogue
Federal Analog Act
The Federal Analog Act, , is a controversial section of the United States Controlled Substances Act which allowed any chemical "substantially similar" to a controlled substance listed in Schedule I or II to be treated as if it were also listed in those schedules, but only if intended for human...
in several countries such as Australia
Australia
Australia , officially the Commonwealth of Australia, is a country in the Southern Hemisphere comprising the mainland of the Australian continent, the island of Tasmania, and numerous smaller islands in the Indian and Pacific Oceans. It is the world's sixth-largest country by total area...
and New Zealand
New Zealand
New Zealand is an island country in the south-western Pacific Ocean comprising two main landmasses and numerous smaller islands. The country is situated some east of Australia across the Tasman Sea, and roughly south of the Pacific island nations of New Caledonia, Fiji, and Tonga...
. As of the 4th November 2010, the UK Home Office
Home Office
The Home Office is the United Kingdom government department responsible for immigration control, security, and order. As such it is responsible for the police, UK Border Agency, and the Security Service . It is also in charge of government policy on security-related issues such as drugs,...
announced a ban on the importation of 2-DPMP, following a recommendation from the ACMD.
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
Emergency department
An emergency department , also known as accident & emergency , emergency room , emergency ward , or casualty department is a medical treatment facility specialising in acute care of patients who present without prior appointment, either by their own means or by ambulance...
visits which prompted the UK government to commission a review from the ACMD One man had ingested nearly 1 gram of the drug and this would 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)."