Troparil (also known as (–)-2β-Carbomethoxy-3β-phenyltropane, WIN 35,065-2, or β-CPT) is a
stimulant
Stimulants (also often referred to as psychostimulants or colloquially as uppers) is an overarching term that covers many drugs including those that increase activity of the central nervous system and the body, drugs that are pleasurable and inv ...
drug used in scientific research. Troparil is a
phenyltropane
Phenyltropanes (PTs) were originally developed to reduce cocaine addiction and dependency. In general these compounds act as inhibitors of the plasmalemmal monoamine reuptake transporters. Although RTI holds a strong position in this field, the ...
-based
dopamine reuptake inhibitor
A dopamine reuptake inhibitor (DRI) is a class of drug which acts as a reuptake inhibitor of the monoamine neurotransmitter dopamine by blocking the action of the dopamine transporter (DAT). Reuptake inhibition is achieved when extracellular dopa ...
(DRI) that is derived from
methylecgonidine
Methylecgonidine (anhydromethylecgonine; anhydroecgonine methyl ester; AEME) is a chemical intermediate derived from ecgonine or cocaine.
Methylecgonidine is a pyrolysis product formed when crack cocaine is smoked, making this substance a useful ...
. Troparil is a few times more potent than
cocaine
Cocaine (from , from , ultimately from Quechuan languages, Quechua: ''kúka'') is a central nervous system (CNS) stimulant mainly recreational drug use, used recreationally for its euphoria, euphoric effects. It is primarily obtained from t ...
as a dopamine reuptake inhibitor, but is less potent as a serotonin reuptake inhibitor, and has a duration spanning a few times longer, since the phenyl ring is directly connected to the tropane ring through a non-hydrolyzable carbon-carbon bond. The lack of an ester linkage removes the
local anesthetic
A local anesthetic (LA) is a medication that causes absence of pain sensation. In the context of surgery, a local anesthetic creates an absence of pain in a specific location of the body without a loss of consciousness, as opposed to a general an ...
action from the drug, so troparil is a pure stimulant. This change in activity also makes troparil slightly less
cardiotoxic
Cardiotoxicity is the occurrence of heart dysfunction as electric or muscle damage, resulting in heart toxicity. The heart becomes weaker and is not as efficient in pumping blood. Cardiotoxicity may be caused by chemotherapy (a usual example is th ...
than cocaine. The most commonly used form of troparil is the
tartrate
A tartrate is a salt or ester of the organic compound tartaric acid, a dicarboxylic acid. The formula of the tartrate dianion is O−OC-CH(OH)-CH(OH)-COO− or C4H4O62−.
The main forms of tartrates used commercially are pure crystalline ta ...
salt
Salt is a mineral composed primarily of sodium chloride (NaCl), a chemical compound belonging to the larger class of salts; salt in the form of a natural crystalline mineral is known as rock salt or halite. Salt is present in vast quantitie ...
, but the
hydrochloride
In chemistry, a hydrochloride is an acid salt resulting, or regarded as resulting, from the reaction of hydrochloric acid with an organic base (e.g. an amine). An alternative name is chlorhydrate, which comes from French. An archaic alternative na ...
and
naphthalenedisulfonate salts are also available, as well as the free base.
Background
The first known published synthesis of troparil and the related compound
WIN 35428
(–)-2-β-Carbomethoxy-3-β-(4-fluorophenyl)tropane (β-CFT, WIN 35,428) is a stimulant drug used in scientific research. CFT is a phenyltropane based dopamine reuptake inhibitor and is structurally derived from cocaine. It is around 3-10x more ...
is by Clarke and co-workers during the 1970s.
[ Apparently, it was their intention to separate the stimulant actions of cocaine from its toxicity and dependence liability. Troparil is the only regular ]phenyltropane
Phenyltropanes (PTs) were originally developed to reduce cocaine addiction and dependency. In general these compounds act as inhibitors of the plasmalemmal monoamine reuptake transporters. Although RTI holds a strong position in this field, the ...
having a NET
Net or net may refer to:
Mathematics and physics
* Net (mathematics), a filter-like topological generalization of a sequence
* Net, a linear system of divisors of dimension 2
* Net (polyhedron), an arrangement of polygons that can be folded up ...
affinity that exceeds the DAT affinity.
Application
Phenyltropanes are likely to have less abuse and dependency compared with cocaine.
Troparil is used in scientific research into the dopamine
Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...
reuptake transporter. 3H-radiolabelled
Isotopic labeling (or isotopic labelling) is a technique used to track the passage of an isotope (an atom with a detectable variation in neutron count) through a reaction, metabolic pathway, or cell. The reactant is 'labeled' by replacing specific ...
forms of troparil have been used in humans and animals to map the distribution of dopamine
Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...
transporters in the brain
A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...
. It is also used for animal research into stimulant drugs as an alternative to cocaine which produces similar effects, but avoids the stringent licensing requirements for the use of cocaine itself.
Troparil has similar effects to cocaine in animal studies, but recreational use of this compound to date has proven extremely rare. Despite being easily made by the reaction of methylecgonidine
Methylecgonidine (anhydromethylecgonine; anhydroecgonine methyl ester; AEME) is a chemical intermediate derived from ecgonine or cocaine.
Methylecgonidine is a pyrolysis product formed when crack cocaine is smoked, making this substance a useful ...
with phenylmagnesium bromide
Phenylmagnesium bromide, with the simplified formula , is a magnesium-containing organometallic compound. It is commercially available as a solution in diethyl ether or tetrahydrofuran (THF). Phenylmagnesium bromide is a Grignard reagent. It is o ...
, the relative scarcity of methylecgonidine and the demanding reaction conditions required for the synthesis put production of this compound beyond the capacity of most illicit drug manufacturers, and legitimate supplies of troparil are available only in very small quantities for a very high price.
Legality
The legal status of troparil is unclear, but it may be considered a controlled substance analog
A designer drug is a structural analog, structural or Functional analog (chemistry), functional analog of a controlled substance that has been designed to mimic the pharmacological effects of the original drug, while avoiding classification as ill ...
of cocaine in the United States
The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territorie ...
on the grounds of its related chemical structure. The legal status of troparil and many other cocaine analogs in Canada, is dependent on if ecgonine, coca, or cocaine were derivatives of the compound, according to the wording on the entry of coca in Schedule 1 of the Controlled Drugs and Substances Act
The ''Controlled Drugs and Substances Act'' (french: Loi réglementant certaines drogues et autres substances) (the ''Act'') is Canada's federal drug control statute. Passed in 1996 under Prime Minister Jean Chrétien's government, it repeals ...
.
See also
* List of phenyltropanes
* List of cocaine analogues
This is a list of cocaine analogues. A cocaine analogue is an (usually) artificial construct of a novel chemical compound from (often the starting point of natural) cocaine's molecular structure, with the result product sufficiently similar to co ...
* Amfonelic acid
References
{{Phenyltropanes
Tropanes
WIN compounds
Dopamine reuptake inhibitors
Stimulants
Sympathomimetic amines
Phenyl compounds