Substituted naphthylethylamine

The substituted naphthylethylamines are a class of chemical compounds based on naphthalene. Many naphthylethylamines are naphthylaminopropanes (also known as naphthylisopropylamines) due to the presence of a methyl group at the alpha carbon of the alkyl chain. The naphthylethylamines are derivatives of the phenethylamines, while the naphthylaminopropanes are derivatives of the amphetamines.

2-Naphthylaminopropane, one of the more well-known naphthylethylamines.

1-Naphthylaminopropane, a lesser-known naphthylethylamine.

There are two types of naphthylethylamines based on positional isomerism: 1-naphthylethylamines and 2-naphthylethylamines. Examples of these include 1-naphthylaminopropane (1-NAP) and 2-naphthylaminopropane (2-NAP), respectively.

List of substituted naphthylethylamines

The substituted napthylethylamines include the following compounds:^[1][2][3]

• 1-Naphthylaminopropane (1-NAP; α-NAP)^[3]
• 2-Naphthylaminopropane (2-NAP; β-NAP; NAP; naphthylisopropylamine; PAL-287)^[1][3]
• Methylnaphthylaminopropane (MNAP; methamnetamine; PAL-1046)^[1]
• Ethylnaphthylaminopropane (ENAP; PAL-1045)^[1]
• Naphthylpropylaminopentane (NPAP)^[4]
• 1-Naphthylmethcathinone (AMAPN)^[2]
• 2-Naphthylmethcathinone (BMAPN; βk-MNAP)^[2]
• Agomelatine (7-methoxy-N-acetyl-1-naphthylethylamine)
• Napactadine (DL-588)
• PRC200-SS
• Pronethalol (β-hydroxy-N-isopropyl-2-naphthylethylamine)
• Naphthylmorpholine (PAL-678)^[5]
• Naphthylmetrazine (PAL-704)^[5]
• Naphyrone ("naphthylpyrovalerone")
• Methylnaphthidate (HDMP-28; "naphthylmethylphenidate")
• Ethylnaphthidate (HDEP-28; "naphthylethylphenidate")
• G-N (1,4-dimethoxynaphthyl-2-isopropylamine)
• 2C-G-N (1,4-dimethoxynaphthyl-2-ethylamine)

Additional naphthylethylamines include 4-NEMD, centanafadine (EB-1020), nafimidone, naphazoline, and xaliproden (SR-57746). Some synthetic cannabinoids such as THJ-018 and THJ-2201 are also naphthylethylamines.

Related compounds

Some related compounds that are not technically naphthylethylamines include 1-naphthylpiperazine and its derivatives like CSP-2503, F-11,461, S-14506, and S-14671. Another related compound is 2-naphthylpiperazine. DMNPC is a 2-naphthylpiperidine.

Pharmacology

Many naphthylethylamines, like 2-naphthylaminopropane and derivatives, act as monoamine releasing agents (MRAs), monoamine reuptake inhibitors (MRIs), and/or monoamine receptor modulators.^[1][5] Naphthylpropylaminopentane (NPAP) is a monoaminergic activity enhancer (MAE).^[4] Some, such as 2-naphthylaminopropane and to a lesser extent 1-naphthylaminopropane, but not others, such as NPAP, are also variably potent monoamine oxidase inhibitors (MAOIs).^[3][4]

Monoamine release of naphthylethylamines (EC₅₀Tooltip Half maximal effective concentration, nM)

Compound	NETooltip Norepinephrine	DATooltip Dopamine	5-HTTooltip Serotonin	Ref
d-Amphetamine	6.6–10.2	5.8–24.8	698–1,765	[6][7][8][9][10]
1-Naphthylaminopropane	ND	ND	ND	ND
2-Naphthylaminopropane (NAP; PAL-287)	11.1	12.6	3.4	[11][8]
d-Methamphetamine	12.3–14.3	8.5–40.4	736–1,292	[6][12][8][10]
Methylnaphthylaminopropane (MNAP; PAL-1046)	34	10	13	[13][14]
l-Methcathinone	13.1	14.8	1,772	[15][9]
1-Naphthylmethcathinone (AMAPN)	92% at 10 μM	55	21	[2][16]
2-Naphthylmethcathinone (BMAPN; βk-MNAP)	94% at 10 μM	34	27	[2][16]
d-Ethylamphetamine	28.8	44.1	333.0	[17][18]
Ethylnaphthylaminopropane (ENAP; PAL-1045)	137	46 a	12 a	[13]
2-Phenylmorpholine (PAL-632)	79	86	20,260	[5]
Naphthylmorpholine (PAL-678)	88% at 10 μM	79% at 10 μM	92% at 10 μM	[5]
Phenmetrazine	29–50.4	70–131	7,765–>10,000	[19][8][20][5]
Naphthylmetrazine (PAL-704)	203	111	RI (105)	[5]
Notes: The smaller the value, the more strongly the drug releases the neurotransmitter. The assays were done in rat brain synaptosomes and human potencies may be different. See also Monoamine releasing agent § Activity profiles for a larger table with more compounds. Footnotes: a ENAPTooltip Ethylnaphthylaminopropane is a partial releaser of serotonin (EmaxTooltip maximal efficacy = 66%) and dopamine (Emax = 78%). Refs: [21][22]