2-Benzylpiperidine

Last updated
2-Benzylpiperidine
2-Benzylpiperidine.png
2-benzylpiperidine3d.png
Clinical data
Routes of
administration
Oral
ATC code
  • none
Legal status
Legal status
  • In general: uncontrolled
Identifiers
  • 2-benzylpiperidine
CAS Number
PubChem CID
ChemSpider
ECHA InfoCard 100.046.581 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C12H17N
Molar mass 175.275 g·mol−1
3D model (JSmol)
  • C1CCNC(C1)CC2=CC=CC=C2
  • InChI=1S/C12H17N/c1-2-6-11(7-3-1)10-12-8-4-5-9-13-12/h1-3,6-7,12-13H,4-5,8-10H2 Yes check.svgY
  • Key:ITXCORRITGNIHP-UHFFFAOYSA-N Yes check.svgY
   (verify)

2-Benzylpiperidine is a stimulant drug of the piperidine class. It is similar in structure to other drugs such as methylphenidate and desoxypipradrol but around one twentieth as potent, and while it boosts norepinephrine levels to around the same extent as d-amphetamine, [1] it has very little effect on dopamine levels, with its binding affinity for the dopamine transporter around 175 times lower than for the noradrenaline transporter. [2] 2-benzylpiperidine is little used as a stimulant, with its main use being as a synthetic intermediate in the manufacture of other drugs. [3] [4] [5]

See also

Related Research Articles

<span class="mw-page-title-main">Amphetamine</span> Central nervous system stimulant

Amphetamine is a strong central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. It is also commonly used as a recreational drug. Amphetamine was discovered in 1887 and exists as two enantiomers: levoamphetamine and dextroamphetamine. Amphetamine properly refers to a specific chemical, the racemic free base, which is equal parts of the two enantiomers in their pure amine forms. The term is frequently used informally to refer to any combination of the enantiomers, or to either of them alone. Historically, it has been used to treat nasal congestion and depression. Amphetamine is also used as an athletic performance enhancer and cognitive enhancer, and recreationally as an aphrodisiac and euphoriant. It is a prescription drug in many countries, and unauthorized possession and distribution of amphetamine are often tightly controlled due to the significant health risks associated with recreational use.

<span class="mw-page-title-main">Stimulant</span> Overarching term covers many drugs that increase activity of the central nervous system

Stimulants 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 invigorating, or drugs that have sympathomimetic effects. Stimulants are widely used throughout the world as prescription medicines as well as without a prescription as performance-enhancing or recreational drugs. Among narcotics, stimulants produce a noticeable crash or comedown at the end of their effects. The most frequently prescribed stimulants as of 2013 were lisdexamfetamine (Vyvanse), methylphenidate (Ritalin), and amphetamine (Adderall). It was estimated in 2015 that the percentage of the world population that had used cocaine during a year was 0.4%. For the category "amphetamines and prescription stimulants" the value was 0.7%, and for MDMA 0.4%.

<span class="mw-page-title-main">Methylphenidate</span> Central nervous system stimulant

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, narcolepsy. It is a primary medication for ADHD; it may be taken by mouth or applied to the skin, and different formulations have varying durations of effect, commonly ranging from 2–4 hours. Though there is little to no evidence, and in some cases contradictory evidence, to support its use as an athletic performance enhancer, cognitive enhancer, aphrodisiac or euphoriant, claims persist that it can be used for these purposes.

<span class="mw-page-title-main">Monoamine transporter</span>

Monoamine transporters (MATs) are protein structures that function as integral plasma-membrane transporters to regulate concentrations of extracellular monoamine neurotransmitters. Three major classes of MATs are responsible for the reuptake of their associated amine neurotransmitters. MATs are located just outside the synaptic cleft (peri-synaptically), transporting monoamine transmitter overflow from the synaptic cleft back to the cytoplasm of the pre-synaptic neuron. MAT regulation generally occurs through protein phosphorylation and posttranslational modification. Due to their significance in neuronal signaling, MATs are commonly associated with drugs used to treat mental disorders as well as recreational drugs. Compounds targeting MATs range from medications such as the wide variety of tricyclic antidepressants, selective serotonin reuptake inhibitors such as fluoxetine (Prozac) to stimulant medications such as methylphenidate (Ritalin) and amphetamine in its many forms and derivatives methamphetamine (Desoxyn) and lisdexamfetamine (Vyvanse). Furthermore, drugs such as MDMA and natural alkaloids such as cocaine exert their effects in part by their interaction with MATs, by blocking the transporters from mopping up dopamine, serotonin, and other neurotransmitters from the synapse.

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 dopamine not absorbed by the postsynaptic neuron is blocked from re-entering the presynaptic neuron. This results in increased extracellular concentrations of dopamine and increase in dopaminergic neurotransmission.

<span class="mw-page-title-main">Phenyltropane</span> Class of chemical compounds

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, they are not the only researchers that have prepared these analogues. This research has spanned beyond the last couple decades, and has picked up its pace in recent times, creating numerous phenyltropanes as research into cocaine analogues garners interest to treat addiction.

<span class="mw-page-title-main">(+)-CPCA</span> Stimulant drug

(+)-CPCA is a stimulant drug similar in structure to pethidine and to RTI-31, but nocaine is lacking the two-carbon bridge of RTI-31's tropane skeleton. This compound was first developed as a substitute agent for cocaine.

A serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI), also known as a triple reuptake inhibitor (TRI), is a type of drug that acts as a combined reuptake inhibitor of the monoamine neurotransmitters serotonin, norepinephrine, and dopamine. It does this by concomitantly inhibiting the serotonin transporter (SERT), norepinephrine transporter (NET), and dopamine transporter (DAT), respectively. Inhibition of the reuptake of these neurotransmitters increases their extracellular concentrations and, therefore, results in an increase in serotonergic, adrenergic, and dopaminergic neurotransmission.

<span class="mw-page-title-main">Troparil</span> Chemical compound

Troparil is a stimulant drug used in scientific research. Troparil is a phenyltropane-based dopamine reuptake inhibitor (DRI) that is derived from methylecgonidine. Troparil is a few times more potent than cocaine 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 action from the drug, so troparil is a pure stimulant. This change in activity also makes troparil slightly less cardiotoxic than cocaine. The most commonly used form of troparil is the tartrate salt, but the hydrochloride and naphthalenedisulfonate salts are also available, as well as the free base.

<span class="mw-page-title-main">HDMP-28</span> Chemical compound

HDMP-28 or methylnaphthidate is a piperidine based stimulant drug, closely related to methylphenidate, but with the benzene ring replaced by naphthalene. It is a potent dopamine reuptake inhibitor, with several times the potency of methylphenidate and a short duration of action, and is a structural isomer of another potent dopamine reuptake inhibitor, N,O-Dimethyl-4-(2-naphthyl)piperidine-3-carboxylate.

<span class="mw-page-title-main">RTI-126</span> Pharmaceutical drug

RTI-126 is a phenyltropane derivative which acts as a potent monoamine reuptake inhibitor and stimulant drug, and has been sold as a designer drug. It is around 5 times more potent than cocaine at inhibiting monoamine reuptake in vitro, but is relatively unselective. It binds to all three monoamine transporters, although still with some selectivity for the dopamine transporter. RTI-126 has a fast onset of effects and short duration of action, and its pharmacological profile in animals is among the closest to cocaine itself out of all the drugs in the RTI series. Its main application in scientific research has been in studies investigating the influence of pharmacokinetics on the abuse potential of stimulant drugs, with its rapid entry into the brain thought to be a key factor in producing its high propensity for development of dependence in animals.

<span class="mw-page-title-main">O-2172</span> Chemical compound

O-2172 is a drug developed by Organix Inc, which acts as a stimulant and potent dopamine reuptake inhibitor. It is an analogue of methylphenidate where the phenyl ring has had a 3,4-dichloro substitution added, and the piperidine ring has been replaced by cyclopentane. It is around 1/3 the potency of methylphenidate, demonstrating that even with the important binding group of the nitrogen lone pair removed entirely, selective DAT binding and reuptake inhibition is still possible.

<span class="mw-page-title-main">RTI-113</span> Chemical compound

RTI(-4229)-113 is a stimulant drug which acts as a potent and fully selective dopamine reuptake inhibitor (DRI). It has been suggested as a possible substitute drug for the treatment of cocaine addiction. "RTI-113 has properties that make it an ideal medication for cocaine abusers, such as an equivalent efficacy, a higher potency, and a longer duration of action as compared to cocaine." Replacing the methyl ester in RTI-31 with a phenyl ester makes the resultant RTI-113 fully DAT specific. RTI-113 is a particularly relevant phenyltropane cocaine analog that has been tested on squirrel monkeys. RTI-113 has also been tested against cocaine in self-administration studies for DAT occupancy by PET on awake rhesus monkeys. The efficacy of cocaine analogs to elicit self-administration is closely related to the rate at which they are administered. Slower onset of action analogs are less likely to function as positive reinforcers than analogues that have a faster rate of onset.

<span class="mw-page-title-main">Arylcyclohexylamine</span> Class of chemical compounds

Arylcyclohexylamines, also known as arylcyclohexamines or arylcyclohexanamines, are a chemical class of pharmaceutical, designer, and experimental drugs.

<span class="mw-page-title-main">3,4-Dichloromethylphenidate</span> Chemical compound

3,4-Dichloromethylphenidate is a stimulant drug related to methylphenidate. Dichloromethylphenidate is a potent psychostimulant that acts as both a dopamine reuptake inhibitor and norepinephrine reuptake inhibitor, meaning it effectively boosts the levels of the norepinephrine and dopamine neurotransmitters in the brain, by binding to, and partially blocking the transporter proteins that normally remove those monoamines from the synaptic cleft.

<span class="mw-page-title-main">4-Methylmethylphenidate</span> Chemical compound

threo-4-Methylmethylphenidate (4-MeTMP) is a stimulant drug related to methylphenidate. It is slightly less potent than methylphenidate and has relatively low efficacy at blocking dopamine reuptake despite its high binding affinity, which led to its investigation as a possible substitute drug for treatment of stimulant abuse. On the other hand, several other simple ring-substituted derivatives of threo-methylphenidate such as the 4-fluoro and 3-chloro compounds are more potent than methylphenidate both in efficacy as dopamine reuptake inhibitors and in animal drug discrimination assays.

<span class="mw-page-title-main">1-Benzyl-4-(2-(diphenylmethoxy)ethyl)piperidine</span> Chemical compound

1-Benzyl-4-(2- ​ethyl)​piperidine is a stimulant of the piperidine class which acts as a potent and selective dopamine reuptake inhibitor. It is closely related to vanoxerine and GBR-12,935, which in contrast are piperazines.

<span class="mw-page-title-main">4-Fluoromethylphenidate</span> Chemical compound

4-Fluoromethylphenidate is a stimulant drug that acts as a higher potency dopamine reuptake inhibitor than the closely related methylphenidate.

<span class="mw-page-title-main">Substituted phenylmorpholine</span> Class of chemical compounds

Substituted phenylmorpholines, or substituted phenmetrazines alternatively, are chemical derivatives of phenylmorpholine or of the psychostimulant drug phenmetrazine. Most such compounds act as releasers of monoamine neurotransmitters, and have stimulant effects. Some also act as agonists at serotonin receptors, and compounds with an N-propyl substitution act as dopamine receptor agonists. A number of derivatives from this class have been investigated for medical applications, such as for use as anorectics or medications for the treatment of ADHD. Some compounds have also become subject to illicit use as designer drugs.

References

  1. Ferris RM, Tang FL (September 1979). "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". The Journal of Pharmacology and Experimental Therapeutics. 210 (3): 422–8. PMID   39160.
  2. Kim DI, Deutsch HM, Ye X, Schweri MM (May 2007). "Synthesis and pharmacology of site-specific cocaine abuse treatment agents: restricted rotation analogues of methylphenidate". Journal of Medicinal Chemistry. 50 (11): 2718–31. doi:10.1021/jm061354p. PMID   17489581.
  3. Ablordeppey SY, Fischer JB, Law H, Glennon RA (August 2002). "Probing the proposed phenyl-A region of the sigma-1 receptor". Bioorganic & Medicinal Chemistry. 10 (8): 2759–65. doi:10.1016/S0968-0896(02)00096-2. PMID   12057665.
  4. Ágai B, Proszenyák A, Tárkányi G, Vida L, Faigl F (2004). "Convenient, Benign and Scalable Synthesis of 2- and 4-Substituted Benzylpiperidines". European Journal of Organic Chemistry. 2004 (17): 3623–3632. doi:10.1002/ejoc.200400215.
  5. US 6124317,Bigge CF, Keana JR, Cai SX, Weber E, Woodward R, Lan NC, Guzikowski AP,"2-substituted piperidine analogs and their use as subtype-selective NMDA receptor antagonists."