Clinical data | |
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Trade names | Bontril |
AHFS/Drugs.com | Monograph |
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Routes of administration | Oral |
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Pharmacokinetic data | |
Bioavailability | Peak plasma levels occur within 1 to 3 hours. Absorption is usually complete by 4 to 6 hours |
Metabolism | Hepatic |
Elimination half-life | 19-24 hours |
Excretion | Urinary elimination |
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ECHA InfoCard | 100.010.186 |
Chemical and physical data | |
Formula | C12H17NO |
Molar mass | 191.274 g·mol−1 |
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Phendimetrazine (Bontril, Adipost, Anorex-SR, Appecon, Melfiat, Obezine, Phendiet, Plegine, Prelu-2, Statobex) is a stimulant drug of the morpholine chemical class used as an appetite suppressant. [2]
Phendimetrazine functions as a prodrug to phenmetrazine; approximately 30 percent of an oral dose is converted into it. Phendimetrazine can essentially be thought of as an extended-release formulation of phenmetrazine with less potential for abuse. Phendimetrazine is an anorectic drug which acts as a norepinephrine-dopamine releasing agent (NDRA). [3]
As an amphetamine congener, its structure incorporates the backbone of methamphetamine, a potent CNS stimulant. While the addition of an N-methyl group to amphetamine significantly increases its potency and bioavailability, methylation of phenmetrazine renders the compound virtually inactive. However, phendimetrazine is a prodrug for phenmetrazine which acts as the active metabolite. Phendimetrazine possesses preferable pharmacokinetics over phenmetrazine as a therapeutic agent because its metabolization by demethylases produces a more steady and prolonged exposure of active drug within the body. This decreases abuse potential as the peak blood-concentration of active phenmetrazine that's produced from a single dose of phendimetrazine is lower than a single therapeutically equivalent dose of phenmetrazine.
Indicated as a short-term secondary treatment for exogenous obesity, phendimetrazine immediate-release 35mg tablets are typically consumed one hour before meals, not to exceed three doses daily. Phendimetrazine is also manufactured as a 105mg extended-release capsule for once daily dosing, typically consumed 30 to 60 minutes before a morning meal. Whereas the immediate-release formulation has a maximum daily dosage of 210mg (6 tablets), the extended-release capsules have a maximum daily dosage of 105mg (one capsule).
According to the List of Psychotropic Substances under International Control published by the International Narcotics Control Board, phendimetrazine is a Schedule III controlled substance under the Convention on Psychotropic Substances. [4]
Alkylation of ephedrine (1) with oxirane (2) gives the diol, N-(2-Hydroxyethyl) Pseudoephedrine [54275-43-3] [91688-17-4] (3). (The secondary nature of the amine in 1) eliminates the complication of dialkylation and thus the need to go through the amide.) Cyclization affords phendimetrazine (4).
The halogenation of Propiophenone [93-55-0] (1) with bromine gives 2-Bromopropiophenone [2114-00-3] (2). Further reaction with N-Methylethanolamine [109-83-1] (3) goes on to five CID:232614 [902267-47-4] (4). Cyclization with formic acid completed the synthesis of phendimetrazine (5).
The reaction between Ephedrine [299-42-3] (1) and ethyl chloroacetate [105-39-5] (2) in the presence of sodium hydride gives 4,5-dimethyl-6-phenylmorpholin-3-one, [5493-96-9] (3). The optional reduction of the lactam carbonyl with lithium aluminium hydride.
Additional method: [10]
Amphetamine is a central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. Amphetamine was discovered as a chemical in 1887 by Lazăr Edeleanu, and then as a drug in the late 1920s. It 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.
Stimulants are a class of drugs that increase the activity of the brain and the spinal cord. They are used for various purposes, such as enhancing alertness, attention, motivation, cognition, mood, and physical performance. Some of the most common stimulants are caffeine, nicotine, amphetamines, cocaine, and modafinil.
Ephedrine is a central nervous system (CNS) stimulant that is often used to prevent low blood pressure during anesthesia. It has also been used for asthma, narcolepsy, and obesity but is not the preferred treatment. It is of unclear benefit in nasal congestion. It can be taken by mouth or by injection into a muscle, vein, or just under the skin. Onset with intravenous use is fast, while injection into a muscle can take 20 minutes, and by mouth can take an hour for effect. When given by injection it lasts about an hour and when taken by mouth it can last up to four hours.
Methcathinone is a monoamine alkaloid and psychoactive stimulant, a substituted cathinone. It is used as a recreational drug due to its potent stimulant and euphoric effects and is considered to be addictive, with both physical and psychological withdrawal occurring if its use is discontinued after prolonged or high-dosage administration. It is usually snorted, but can be smoked, injected, or taken orally.
D-norpseudoephedrine, also known as cathine and (+)-norpseudoephedrine, is a psychoactive drug of the phenethylamine and amphetamine chemical classes which acts as a stimulant. Along with cathinone, it is found naturally in Catha edulis (khat), and contributes to its overall effects. It has approximately 7-10% the potency of amphetamine.
Phenylpropanolamine (PPA) is a sympathomimetic agent which is used as a decongestant and appetite suppressant. It was commonly used in prescription and over-the-counter cough and cold preparations. In veterinary medicine, it is used to control urinary incontinence in dogs.
Phenmetrazine is a stimulant drug first synthesized in 1952 and originally used as an appetite suppressant, but withdrawn from the market in the 1980s due to widespread abuse. It was initially replaced by its analogue phendimetrazine which functions as a prodrug to phenmetrazine, but now it is rarely prescribed, due to concerns of abuse and addiction. Chemically, phenmetrazine is a substituted amphetamine containing a morpholine ring.
Armodafinil (trade name Nuvigil) is the enantiopure compound of the eugeroic modafinil (Provigil). It consists of only the (R)-(−)-enantiomer of the racemic modafinil. Armodafinil is produced by the pharmaceutical company Cephalon Inc. and was approved by the U.S. Food and Drug Administration (FDA) in June 2007. In 2016, the FDA granted Mylan rights for the first generic version of Cephalon's Nuvigil to be marketed in the U.S.
Amfepramone, also known as diethylpropion, is a stimulant drug of the phenethylamine, amphetamine, and cathinone classes that is used as an appetite suppressant. It is used in the short-term management of obesity, along with dietary and lifestyle changes. Amfepramone has a similar chemical structure to the antidepressant and smoking cessation aid bupropion, which has also been developed as a weight-loss medicine when in a combination product with naltrexone.
Lisdexamfetamine, most commonly sold under the brand name Vyvanse and Elvanse among others, is a stimulant medication that is used to treat attention deficit hyperactivity disorder (ADHD) in children and adults and for moderate-to-severe binge eating disorder in adults. Lisdexamfetamine is taken by mouth. Its effects generally begin within two hours and last for up to 14 hours. In the United Kingdom, it is usually less preferred to methylphenidate for the treatment of children.
Etilamfetamine is a stimulant drug of the phenethylamine and amphetamine chemical classes. It was invented in the early 20th century and was subsequently used as an anorectic or appetite suppressant in the 1950s, but was not as commonly used as other amphetamines such as amphetamine, methamphetamine, and benzphetamine, and was largely discontinued once newer drugs such as phenmetrazine were introduced. It most likely acts primarily as a dopamine releasing agent. Its activity as a norepinephrine or serotonin releasing agent is not known.
Ethcathinone, also known as ethylpropion or ETH-CAT, is a stimulant drug of the phenethylamine, amphetamine, and cathinone chemical classes. It is an active metabolite of the prodrug diethylcathinone and is fully responsible for its effects. Ethcathinone has been identified as an ingredient in both quasi-legal "party pills", and, along with mephedrone, has also been reported as having been sold as "ecstasy" in the Australian city of Cairns.
The Convention on Psychotropic Substances of 1971 is a United Nations treaty designed to control psychoactive drugs such as amphetamine-type stimulants, barbiturates, benzodiazepines, and psychedelics signed in Vienna, Austria on 21 February 1971. The Single Convention on Narcotic Drugs of 1961 did not ban the many newly discovered psychotropics, since its scope was limited to drugs with cannabis, coca and opium-like effects.
Substituted amphetamines are a class of compounds based upon the amphetamine structure; it includes all derivative compounds which are formed by replacing, or substituting, one or more hydrogen atoms in the amphetamine core structure with substituents. The compounds in this class span a variety of pharmacological subclasses, including stimulants, empathogens, and hallucinogens, among others. Examples of substituted amphetamines are amphetamine (itself), methamphetamine, ephedrine, cathinone, phentermine, mephentermine, tranylcypromine, bupropion, methoxyphenamine, selegiline, amfepramone (diethylpropion), pyrovalerone, MDMA (ecstasy), and DOM (STP).
Fenbutrazate (INN), also known as phenbutrazate (BAN), is a psychostimulant used as an appetite suppressant under the trade names Cafilon, Filon, and Sabacid in Europe, Japan, and Hong Kong. It is a derivative of phenmetrazine and may function as a prodrug due to its similarity to phendimetrazine.
G-130 is a drug with stimulant and anorectic effects, related to phenmetrazine.
Amphetamine and methamphetamine are central nervous system stimulants used to treat a variety of conditions. When used recreationally, they are colloquially known as "speed" or sometimes "crank". Amphetamine was first synthesized in 1887 in Germany by Romanian chemist Lazăr Edeleanu, who named it phenylisopropylamine. Around the same time, Japanese organic chemist Nagai Nagayoshi isolated ephedrine from the Chinese ephedra plant and later developed a method for ephedrine synthesis. Methamphetamine was synthesized from ephedrine in 1893 by Nagayoshi. Neither drug had a pharmacological use until 1934, when Smith, Kline & French began selling amphetamine as an inhaler under the trade name Benzedrine for congestion.
2-Phenyl-3,5-dimethylmorpholine is a drug with stimulant and anorectic effects, related to phenmetrazine. Based on what is known from other phenylmorpholines with similar structure, it likely acts as a norepinephrine-dopamine releasing agent and may produce effects similar or slightly different to phenmetrazine.
Amphetamine type stimulants (ATS) are a group of synthetic drugs that are chemical derivatives of the parent compound alpha-methylphenethylamine, also known as amphetamine. Common ATS includes amphetamine, methamphetamine, ephedrine, pseudoephedrine, 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxyethylamphetamine (MDEA). ATS when used illicitly has street names including ice, meth, crystal, crank, bennies, and speed. Within the group of amphetamine-type stimulants, there are also prescription drugs including mixed amphetamine salts, dextroamphetamine, and lisdexamfetamine.
Serdexmethylphenidate is a prodrug of dexmethylphenidate created by the pharmaceutical company KemPharm. The compound was first approved by the FDA as one of the active ingredients in Azstarys for the treatment of attention deficit hyperactivity disorder (ADHD) in children, adolescents, and adults in March 2021. Serdexmethylphenidate is a prodrug which has a delayed onset of action and a prolonged duration of effects compared to dexmethylphenidate, its parent compound.