Ethylnaphthylaminopropane

Ethylnaphthylaminopropane (ENAP; developmental code name PAL-1045) is a monoamine releasing agent (MRA) of the amphetamine and naphthylaminopropane families that is related to naphthylaminopropane (NAP; PAL-287) and methamnetamine (MNAP; PAL-1046).^[1][2][3] It acts specifically as a serotonin–norepinephrine–dopamine releasing agent (SNDRA).^[2][3] However, ENAP is unusual in being a partial releaser of serotonin and dopamine and a full releaser of norepinephrine.^[1][2][3]

Ethylnaphthylaminopropane

Clinical data
Other names	ENAP; N-Ethylnaphthylaminopropane; N-Ethyl-NAP; PAL-1045; Ethamnetamine; Ethylnaphetamine; ENA; ENT; N-Ethylnaphthylisopropylamine; ENIPA
Identifiers
IUPAC name N-ethyl-1-naphthalen-2-ylpropan-2-amine
PubChem CID	61080203
ChemSpider	38754192
Chemical and physical data
Formula	C15H19N
Molar mass	213.324 g·mol−1
3D model (JSmol)	Interactive image
SMILES CCNC(C)CC1=CC2=CC=CC=C2C=C1
InChI InChI=1S/C15H19N/c1-3-16-12(2)10-13-8-9-14-6-4-5-7-15(14)11-13/h4-9,11-12,16H,3,10H2,1-2H3 Key:HKSRURFPXCLKOG-UHFFFAOYSA-N

The EC₅₀Tooltip half-maximal effective concentration (E_maxTooltip maximal efficacy) values of ENAP in terms of monoamine release induction are 12 nM (66%) for serotonin, 46 nM (78%) for dopamine, and 137 nM (94%) for norepinephrine in rat brain synaptosomes.^[2][3] In contrast to NAP and MNAP, which produce clearly dose-dependent increases in locomotor stimulation and brain monoamine levels in rodents, ENAP has been found to show attenuated monoamine elevations and a "flat" dose–response curve.^[4][3] Relatedly, it may have less misuse liability than other drugs like amphetamine, although more research is necessary to assess this possibility.^[4][3]

In addition to its MRA activity, ENAP has been found to be an effective pharmacological chaperone for rescuing misfolded mutant monoamine transporters (MATs).^[5][6]

Monoamine release of ethylnaphthylaminopropane and related agents (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	[7][8][9][10][11]
Naphthylaminopropane (NAP; PAL-287)	11.1	12.6	3.4	[12][9]
d-Methamphetamine	12.3–14.3	8.5–40.4	736–1,292	[7][13][9][11]
Methylnaphthylaminopropane (MNAP; PAL-1046)	34	10	13	[3][2]
l-Methcathinone	13.1	14.8	1,772	[14][10]
2-Naphthylmethcathinone (BMAPN; βk-MNAP)	94% at 10 μM	34	27	[15][16]
d-Ethylamphetamine	28.8	44.1	333.0	[17][18]
Ethylnaphthylaminopropane (ENAP; PAL-1045)	137	46 a	12 a	[3]
Phenmetrazine	29–50.4	70–131	7,765–>10,000	[19][9][20][21]
Naphthylmetrazine (PAL-704)	203	111	RI (105)	[21]
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 ENAP is a partial releaser of serotonin (EmaxTooltip maximal efficacy = 66%) and dopamine (Emax = 78%). Refs:[22][23]

See also

• Naphthylpropylaminopentane