Butylamphetamine
{{Short description|Amphetamine derivative and stimulant}}
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| CAS_number = 51799-33-8
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| PubChem = 94547
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| ChemSpiderID = 85320
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| ChEMBL = 1907545
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| synonyms = N-Butylamphetamine; N-(n-Butyl)amphetamine; NBA; PAL-90; 1-Phenyl-2-butylaminopropane; N-Butyl-α-methylphenethylamine
| IUPAC_name = N-(1-phenylpropan-2-yl)butan-1-amine
| C=13 | H=21 | N=1
| SMILES = CCCCNC(C)CC1=CC=CC=C1
| StdInChI = 1S/C13H21N/c1-3-4-10-14-12(2)11-13-8-6-5-7-9-13/h5-9,12,14H,3-4,10-11H2,1-2H3
| StdInChIKey = VIAVBPFRYASSKF-UHFFFAOYSA-N
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Butylamphetamine (code name PAL-90; also known as N-butylamphetamine or NBA) is a psychostimulant of the substituted amphetamine family which was never marketed.{{cite journal | vauthors = Fitzgerald LR, Gannon BM, Walther D, Landavazo A, Hiranita T, Blough BE, Baumann MH, Fantegrossi WE | title = Structure-activity relationships for locomotor stimulant effects and monoamine transporter interactions of substituted amphetamines and cathinones | journal = Neuropharmacology | volume = 245 | issue = | pages = 109827 | date = March 2024 | pmid = 38154512 | doi = 10.1016/j.neuropharm.2023.109827 | pmc = 10842458 | url = | quote = Although the number of amphetamine analogues with different amine substituents is relatively low in recreational drug markets (Cho and Segal, 1994), N-methyl and N-ethyl substitutions are sometimes found. Pharmacological activity of amphetamine-type drugs is decreased substantially if the N-alkyl chain is lengthened beyond ethyl, as previous studies show that N-propylamphetamine and N-butylamphetamine are ∼4-fold and ∼6-fold less potent than amphetamine in rats (Woolverton et al., 1980).}}{{cite journal | vauthors = Woolverton WL, Shybut G, Johanson CE | title = Structure-activity relationships among some d-N-alkylated amphetamines | journal = Pharmacol Biochem Behav | volume = 13 | issue = 6 | pages = 869–876 | date = December 1980 | pmid = 7208552 | doi = 10.1016/0091-3057(80)90221-x | url = }}
It is the N-butyl analogue of amphetamine and is approximately 6-fold less potent than amphetamine in rats. The drug has been found to be inactive as a dopamine reuptake inhibitor or releasing agent ({{Abbrlink|IC50|half-maximal inhibitory concentration}} and {{Abbrlink|EC50|half-maximal effective concentration}} > 10,000{{nbsp}}nM, respectively).{{cite journal | vauthors = Reith ME, Blough BE, Hong WC, Jones KT, Schmitt KC, Baumann MH, Partilla JS, Rothman RB, Katz JL | title = Behavioral, biological, and chemical perspectives on atypical agents targeting the dopamine transporter | journal = Drug Alcohol Depend | volume = 147 | issue = | pages = 1–19 | date = February 2015 | pmid = 25548026 | pmc = 4297708 | doi = 10.1016/j.drugalcdep.2014.12.005 | url = | quote = Table 1 shows the transporter activity oftwo sets of compounds, one a set of phenethylamine (i.e., amphetamine) analogs and the other a set of β-keto phenethylamine (i.e., cathinone) analogs. Each set of compounds demonstrates predicable structural trends. Amphetamine is a DA releaser with an EC50 value of 8.7 nM. Modifications that increase the size of amphetamine gradually decreased release potency until the increases caused the activity to change to transport inhibition. Specifically, N-alkylation of amphetamine, going from no alkyl group (amphetamine) to methyl (methamphetamine) to ethyl (PAL-99) decreased EC50 values for release from 8.7 to 24.5 to 88.5 nM.Adding an additional methylene to form the N-propyl analog (PAL-424) caused the compound to become a DAT uptake inhibitor with an IC50 value of 1013 nM. Increasing the size even further to butyl (PAL-90) rendered the compound inactive at the DAT.}} With regard to structure–activity relationships, the potency of N-substituted amphetamine derivatives decreases with increasing chain length in terms of both in vitro and in vivo activity.
The pharmacokinetics of butylamphetamine have been studied in humans.{{cite book | last=Gorrod | first=J.W. | title=Frontiers in Catecholamine Research | chapter=The Metabolism and Excretion of 'Amphetamines' in Man | publisher=Elsevier | date=1973 | isbn=978-0-08-017922-3 | doi=10.1016/b978-0-08-017922-3.50180-5 | pages=945–950}}{{cite journal | vauthors = Beckett AH, Shenoy EV | title = The effect of N-alkyl chain length of stereochemistry on the absorption, metabolism and during excretion of N-alkylamphetamines in man | journal = J Pharm Pharmacol | volume = 25 | issue = 10 | pages = 793–799 | date = October 1973 | pmid = 4151673 | doi = 10.1111/j.2042-7158.1973.tb09943.x | url = }} It can be metabolized by CYP2D6 via ring hydroxylation similarly to amphetamine.{{cite journal | vauthors = Bach MV, Coutts RT, Baker GB | title = Metabolism of N,N-dialkylated amphetamines, including deprenyl, by CYP2D6 expressed in a human cell line | journal = Xenobiotica | volume = 30 | issue = 3 | pages = 297–306 | date = March 2000 | pmid = 10752644 | doi = 10.1080/004982500237686 | url = | quote = Ring hydroxylation was also expected because CYP2D6 can mediate the ring oxidation of other amphetamines such as N-n-butylamphetamine, N-ethylamphetamine and amphetamine (Bach et al. 1999).}}{{cite journal | vauthors = Bach MV, Coutts RT, Baker GB | title = Involvement of CYP2D6 in the in vitro metabolism of amphetamine, two N-alkylamphetamines and their 4-methoxylated derivatives | journal = Xenobiotica | volume = 29 | issue = 7 | pages = 719–732 | date = July 1999 | pmid = 10456690 | doi = 10.1080/004982599238344 | url = }} In addition, butylamphetamine can be N-dealkylated into amphetamine (6–9% excreted in urine after 24{{nbsp}}hours).{{cite journal | vauthors = Beckett AH, Shenoy EV | title = The effect of N-alkyl chain length of stereochemistry on the absorption, metabolism and during excretion of N-alkylamphetamines in man | journal = J Pharm Pharmacol | volume = 25 | issue = 10 | pages = 793–799 | date = October 1973 | pmid = 4151673 | doi = 10.1111/j.2042-7158.1973.tb09943.x | url = }}
See also
References
{{Reflist}}
{{Stimulants}}
{{Monoamine releasing agents}}
{{Phenethylamines}}