Misplaced Pages

#364635

37-568: Examples of NDRAs include phenethylamine , tyramine , amphetamine , methamphetamine , lisdexamfetamine , cathinone , methcathinone , phentermine , propylhexedrine , phenmetrazine , pemoline , 4-methylaminorex , and benzylpiperazine . NDRAs have psychostimulant effects and are used to treat medical conditions like attention-deficit hyperactivity disorder (ADHD), binge eating disorder , obesity , narcolepsy , and for other indications. They are also used to increase motivation and to enhance performance . A closely related type of drug

74-423: A benzene ring through a two-carbon, or ethyl group . It is a colourless liquid at room temperature that has a fishy odor, and is soluble in water, ethanol and ether . Its density is 0.964 g/ml and its boiling point is 195 °C. Upon exposure to air, it combines with carbon dioxide to form a solid carbonate salt . Phenethylamine is strongly basic , pK b = 4.17 (or pK a = 9.83), as measured using

111-484: A chemical reaction . In this terminology, methane is used as a reference of comparison. Using methane as a reference, for each hydrogen atom that is replaced or "substituted" by something else, the molecule can be said to be more highly substituted. For example: The suffix -yl is used in organic chemistry to form names of radicals , either separate species (called free radicals ) or chemically bonded parts of molecules (called moieties ). It can be traced back to

148-446: A moiety in the resultant (new) molecule . (In organic chemistry and biochemistry , the terms substituent and functional group , as well as side chain and pendant group , are used almost interchangeably to describe those branches from the parent structure, though certain distinctions are made in polymer chemistry. In polymers , side chains extend from the backbone structure. In proteins , side chains are attached to

185-444: A runner's high , as both phenethylamine and amphetamine are potent euphoriants . Skydiving has also been shown to induce a marked increase in urinary phenethylamine concentrations. Phenethylamine, being similar to amphetamine in its action at their common biomolecular targets , is a releasing agent of norepinephrine and dopamine . It is roughly equipotent to amphetamine in this regard in vitro . Phenethylamine

222-501: A diagnostic biomarker for ADHD. Thirty minutes of moderate- to high-intensity physical exercise has been shown to induce an increase in urinary phenylacetic acid , the primary metabolite of phenethylamine. Two reviews noted a study where the mean 24 hour urinary phenylacetic acid concentration following just 30 minutes of intense exercise rose 77% above its base level; the reviews suggest that phenethylamine synthesis sharply increases during physical exercise during which it

259-444: A lesser extent, it also acts as a neurotransmitter in the human central nervous system . In mammals, phenethylamine is produced from the amino acid L-phenylalanine by the enzyme aromatic L-amino acid decarboxylase via enzymatic decarboxylation . In addition to its presence in mammals, phenethylamine is found in many other organisms and foods, such as chocolate , especially after microbial fermentation . Phenethylamine

296-406: A portion of the full chemical name. According to the above rules, a carbon atom in a molecule, considered as a substituent, has the following names depending on the number of hydrogens bound to it, and the type of bonds formed with the remainder of the molecule: In a chemical structural formula , an organic substituent such as methyl , ethyl , or aryl can be written as R (or R , R , etc.) It

333-432: A very rapid turnover rate. Endogenous extracellular tissue levels of trace amines measured in the brain are in the low nanomolar range. These low concentrations arise because of their very short half-life. Because of the pharmacological relationship between phenethylamine and amphetamine, the original paper and both reviews suggest that phenethylamine plays a prominent role in mediating the mood-enhancing euphoric effects of

370-458: Is N -methylphenethylamine . One method for preparing β-phenethylamine, set forth in J. C. Robinson and H. R. Snyder's Organic Syntheses (published 1955), involves the reduction of benzyl cyanide with hydrogen in liquid ammonia , in the presence of a Raney-Nickel catalyst , at a temperature of 130 °C and a pressure of 13.8 MPa. Alternative syntheses are outlined in the footnotes to this preparation. A much more convenient method for

407-510: Is 5–10  minutes; endogenously produced PEA in catecholamine neurons has a half-life of roughly 30 seconds. In humans, PEA is metabolized by phenylethanolamine N -methyltransferase (PNMT), monoamine oxidase A ( MAO-A ), monoamine oxidase B ( MAO-B ), the semicarbazide-sensitive amine oxidases (SSAOs) AOC2 and AOC3 , flavin-containing monooxygenase 3 (FMO3), and aralkylamine N-acetyltransferase (AANAT). N -Methylphenethylamine , an isomer of amphetamine ,

SECTION 10

#1732791767365

444-730: Is a monoaminergic activity enhancer (MAE) of serotonin , norepinephrine , and dopamine in addition to its catecholamine-releasing activity. That is, it enhances the action potential -mediated release of these monoamine neurotransmitters . The compound is active as a MAE at much lower concentrations than the concentrations at which it induces the release of catecholamines. The MAE actions of phenethylamine and other MAEs may be mediated by TAAR1 agonism. Synthetic and more potent MAEs like phenylpropylaminopentane (PPAP) and selegiline ( L -deprenyl) have been derived from phenethylamine. Unlike its derivatives norepinephrine (adrenaline) and epinephrine (adrenaline), phenethylamine

481-603: Is a norepinephrine–dopamine reuptake inhibitor (NDRI), for instance methylphenidate . This pharmacology -related article is a stub . You can help Misplaced Pages by expanding it . Phenethylamine Phenethylamine ( PEA ) is an organic compound , natural monoamine alkaloid , and trace amine , which acts as a central nervous system stimulant in humans. In the brain, phenethylamine regulates monoamine neurotransmission by binding to trace amine-associated receptor 1 (TAAR1) and inhibiting vesicular monoamine transporter 2 (VMAT2) in monoamine neurons . To

518-521: Is a generic placeholder, the R derived from radical or rest , which may replace any portion of the formula as the author finds convenient. The first to use this symbol was Charles Frédéric Gerhardt in 1844. The symbol X is often used to denote electronegative substituents such as the halides . One cheminformatics study identified 849,574 unique substituents up to 12 non-hydrogen atoms large and containing only carbon , hydrogen , nitrogen , oxygen , sulfur , phosphorus , selenium , and

555-415: Is inactive as a psychostimulant under normal circumstances due to rapid metabolism by monoamine oxidase (MAO), but can become active in the presence of a monoamine oxidase inhibitor (MAOI). Phenethylamine has been shown to bind to human trace amine-associated receptor 1 (hTAAR1) as an agonist . β-PEA is also an odorant binding TAAR4 in mice thought to mediate predator avoidance. Phenethylamine

592-454: Is inactive as an agonist of the α- and β-adrenergic receptors . According to Alexander Shulgin in PiHKAL , phenethylamine is completely inactive in humans at doses of up to 1,600   mg orally and 50   mg intravenously . This can be attributed to its extremely rapid metabolic breakdown rather than pharmacodynamic inactivity. Although exogenous phenethylamine on its own

629-401: Is inactive, its metabolism can be strongly inhibited and it can thereby become active, showing psychostimulant effects, when combined with a monoamine oxidase inhibitor (MAOI), specifically monoamine oxidase B (MAO-B) inhibitors like selegiline . Oral L -phenylalanine (a precursor of phenethylamine) and/or phenethylamine itself in combination with selegiline has been studied in

666-422: Is needed to distinguish between isomers . Substituents can be a combination of the inductive effect and the mesomeric effect . Such effects are also described as electron-rich and electron withdrawing . Additional steric effects result from the volume occupied by a substituent. The phrases most-substituted and least-substituted are frequently used to describe or compare molecules that are products of

703-408: Is no mechanism of action or biological target that is common to all members of this subclass. Numerous endogenous compounds – including hormones , monoamine neurotransmitters, and many trace amines (e.g., dopamine , norepinephrine , adrenaline , tyramine , and others) – are substituted phenethylamines. Dopamine is simply phenethylamine with a hydroxyl group attached to the 3 and 4 position of

740-426: Is produced in humans via the metabolism of phenethylamine by PNMT. β-Phenylacetic acid is the primary urinary metabolite of phenethylamine and is produced via monoamine oxidase metabolism and subsequent aldehyde dehydrogenase metabolism. Phenylacetaldehyde is the intermediate product which is produced by monoamine oxidase and then further metabolized into β-phenylacetic acid by aldehyde dehydrogenase. When

777-421: Is rapidly metabolized due to its short half-life of roughly 30 seconds. In a resting state, phenethylamine is synthesized in catecholamine neurons from L - phenylalanine by aromatic amino acid decarboxylase at approximately the same rate as dopamine is produced. Monoamine oxidase deaminates primary and secondary amines that are free in the neuronal cytoplasm but not those bound in storage vesicles of

SECTION 20

#1732791767365

814-400: Is sold as a dietary supplement for purported mood and weight loss -related therapeutic benefits ; however, in orally ingested phenethylamine, a significant amount is metabolized in the small intestine by monoamine oxidase B (MAO-B) and then aldehyde dehydrogenase (ALDH), which converts it to phenylacetic acid . This means that for significant concentrations to reach the brain ,

851-431: The alpha carbon atoms of the amino acid backbone.) The suffix -yl is used when naming organic compounds that contain a single bond replacing one hydrogen; -ylidene and -ylidyne are used with double bonds and triple bonds , respectively. In addition, when naming hydrocarbons that contain a substituent, positional numbers are used to indicate which carbon atom the substituent attaches to when such information

888-433: The halogens in a set of 3,043,941 molecules. Fifty substituents can be considered common as they are found in more than 1% of this set, and 438 are found in more than 0.1%. 64% of the substituents are found in only one molecule. The top 5 most common are the methyl , phenyl , chlorine , methoxy , and hydroxyl substituents. The total number of organic substituents in organic chemistry is estimated at 3.1 million, creating

925-465: The HCl salt, and forms a stable crystalline hydrochloride salt with a melting point of 217 °C. Its experimental log P is 1.41. Substituted phenethylamines are a chemical class of organic compounds based upon the phenethylamine structure; the class is composed of all the derivative compounds of phenethylamine which can be formed by replacing, or substituting , one or more hydrogen atoms in

962-400: The benzene ring. Several notable recreational drugs, such as MDMA (ecstasy), methamphetamine , and cathinones , are also members of the class. All of the substituted amphetamines are phenethylamines, as well. Pharmaceutical drugs that are substituted phenethylamines include phenelzine , phenformin , and fanetizole , among many others. The N - methylated derivative of phenethylamine

999-933: The beta-aminoethyl side chain to the phenyl ring is possible. This can be done via Friedel-Crafts acylation with N-protected acyl chlorides when the arene is activated, or by Heck reaction of the phenyl with N-vinyl oxazolone , followed by hydrogenation , or by cross-coupling with beta-amino organozinc reagents, or reacting a brominated arene with beta-aminoethyl organolithium reagents, or by Suzuki cross-coupling . Reviews that cover attention deficit hyperactivity disorder (ADHD) and phenethylamine indicate that several studies have found abnormally low urinary phenethylamine concentrations in ADHD individuals when compared with controls. In treatment-responsive individuals, amphetamine and methylphenidate greatly increase urinary phenethylamine concentration. An ADHD biomarker review also indicated that urinary phenethylamine levels could be

1036-473: The dosage must be higher than for other methods of administration. Some authors postulated its role in people's falling-in-love without substantiating it with any direct evidence. Phenethylamines, or more properly, substituted phenethylamines , are the group of phenethylamine derivatives that contain phenethylamine as a "backbone"; in other words, this chemical class includes derivative compounds that are formed by replacing one or more hydrogen atoms in

1073-413: The initial phenylethylamine concentration in the brain is low, brain levels can be increased 1000-fold when taking a monoamine oxidase inhibitor (MAOI), particularly a MAO-B inhibitor , and by 3–4  times when the initial concentration is high. Substituent In organic chemistry , a substituent is one or a group of atoms that replaces (one or more) atoms, thereby becoming

1110-415: The old name of methanol , "methylene" (from Ancient Greek : μέθυ méthu , 'wine' and ὕλη húlē , 'wood', 'forest'), which became shortened to " methyl " in compound names, from which -yl was extracted. Several reforms of chemical nomenclature eventually generalized the use of the suffix to other organic substituents. The use of the suffix is determined by the number of hydrogen atoms that

1147-755: The phenethylamine core structure with substituents . Many substituted phenethylamines are psychoactive drugs, which belong to a variety of different drug classes, including central nervous system stimulants (e.g., amphetamine ), hallucinogens (e.g., 2,5-dimethoxy-4-methylamphetamine ), entactogens (e.g., 3,4-methylenedioxyamphetamine ), appetite suppressants (e.g. phentermine ), nasal decongestants and bronchodilators (e.g., pseudoephedrine ), antidepressants (e.g. bupropion ), antiparkinson agents (e.g., selegiline ), and vasopressors (e.g., ephedrine ), among others. Many of these psychoactive compounds exert their pharmacological effects primarily by modulating monoamine neurotransmitter systems; however, there

Norepinephrine–dopamine releasing agent - Misplaced Pages Continue

1184-433: The phenethylamine core structure with substituents . The class of substituted phenethylamines includes all substituted amphetamines , and substituted methylenedioxyphenethylamines (MDxx), and contains many drugs which act as empathogens , stimulants , psychedelics , anorectics , bronchodilators , decongestants , and/or antidepressants , among others. Phenethylamine is produced by a wide range of species throughout

1221-479: The plant and animal kingdoms, including humans; it is also produced by certain fungi and bacteria (genera: Lactobacillus , Clostridium , Pseudomonas and the family Enterobacteriaceae ) and acts as a potent antimicrobial against certain pathogenic strains of Escherichia coli (e.g., the O157:H7 strain ) at sufficient concentrations. Phenethylamine is a primary amine, the amino-group being attached to

1258-968: The substituent replaces on a parent compound (and also, usually, on the substituent). According to the 1993 IUPAC recommendations: The suffix -ylid ine is encountered sporadically, and appears to be a variant spelling of "-ylidene"; it is not mentioned in the IUPAC guidelines. For multiple bonds of the same type, which link the substituent to the parent group, the infixes -di- , -tri- , -tetra- , etc., are used: -diyl (two single bonds), -triyl (three single bonds), -tetrayl (four single bonds), -diylidene (two double bonds). For multiple bonds of different types, multiple suffixes are concatenated : - ylylidene (one single and one double), -ylylidyne (one single and one triple), -diylylidene (two single and one double). The parent compound name can be altered in two ways: Note that some popular terms such as " vinyl " (when used to mean "polyvinyl") represent only

1295-422: The sympathetic neurone. Similarly, β-PEA would not be completely deaminated in the gut as it is a selective substrate for MAO-B, which is not primarily found in the gut. Brain levels of endogenous trace amines are several hundred-fold below those for the classical neurotransmitters noradrenaline, dopamine, and serotonin , but their rates of synthesis are equivalent to those of noradrenaline and dopamine and they have

1332-439: The synthesis of β-phenethylamine is the reduction of ω-nitrostyrene by lithium aluminium hydride in ether, whose successful execution was first reported by R. F. Nystrom and W. G. Brown in 1948. Phenethylamine can also be produced via the cathodic reduction of benzyl cyanide in a divided cell. Assembling phenethylamine structures for synthesis of compounds such as epinephrine, amphetamines, tyrosine, and dopamine by adding

1369-685: The treatment of depression and has been reported to be effective. Misuse of phenethylamine in combination with selegiline has also been reported. The LD 50 Tooltip median lethal dose values of phenethylamine include 175   mg/kg i.p. in mice, 320   mg/kg s.c. in mice, 100   mg/kg i.v. in mice, 100   mg/kg parenterally in mice, 39   mg/kg intracervically in mice, and 200   mg/kg i.p. in guinea pigs. Its LD Lo values include 800   mg/kg p.o. in rats, 100   mg/kg i.p. in rats, 450   μg/kg s.c. in rats, and 300   mg/kg via an unspecified route in mice. By oral route , phenethylamine's half-life

#364635