Naphthylmorpholine

Naphthylmorpholine (code name PAL-678), also known as 2-(2′-naphthyl)morpholine, is a monoamine releasing agent of the arylmorpholine and naphthylethylamine families.^[1][2] It is the derivative of 2-phenylmorpholine with a 2-naphthalene ring instead of a phenyl ring.^[1][2] Naphthylmorpholine is a close analogue of naphthylmetrazine (PAL-704; a naphthalene analogue of phenmetrazine), but lacks naphthylmetrazine's methyl group at the 3 position of the morpholine ring.^[1][2]

Naphthylmorpholine

Clinical data
Other names	PAL-678; PAL678; 2-(2′-Naphthyl)morpholine; 2-(Naphthalen-2-yl)morpholine
Drug class	Monoamine releasing agent
Identifiers
IUPAC name 2-naphthalen-2-ylmorpholine
CAS Number	1097796-91-2
PubChem CID	43350792
ChemSpider	38116416
Chemical and physical data
Formula	C14H15NO
Molar mass	213.280 g·mol−1
3D model (JSmol)	Interactive image
SMILES C1COC(CN1)C2=CC3=CC=CC=C3C=C2
InChI InChI=1S/C14H15NO/c1-2-4-12-9-13(6-5-11(12)3-1)14-10-15-7-8-16-14/h1-6,9,14-15H,7-8,10H2 Key:AQOVYDDILDIECZ-UHFFFAOYSA-N

The drug is a potent monoamine releasing agent.^[1] Its EC₅₀Tooltip half-maximal effective concentration values for induction of monoamine release have not been reported, but it released 92% of serotonin, 88% of norepinephrine, and 79% of dopamine at a concentration of 10,000 nM in rat brain synaptosomes.^[1] Hence, it appears to act preferentially as a releaser of serotonin and norepinephrine and to a lesser extent of dopamine.^[1]

Monoamine release of naphthylmorpholine 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	[3][4][5][6][7]
Naphthylaminopropane (NAP; PAL-287)	11.1	12.6	3.4	[8][5]
d-Methamphetamine	12.3–14.3	8.5–40.4	736–1,292	[3][9][5][7]
Methylnaphthylaminopropane (MNAP; PAL-1046)	34	10	13	[10][11]
l-Methcathinone	13.1	14.8	1,772	[12][6]
2-Naphthylmethcathinone (BMAPN; βk-MNAP)	94% at 10 μM	34	27	[13][14]
d-Ethylamphetamine	28.8	44.1	333.0	[15][16]
Ethylnaphthylaminopropane (ENAP; PAL-1045)	137	46 a	12 a	[10]
2-Phenylmorpholine (PAL-632)	79	86	20,260	[1]
Naphthylmorpholine (PAL-678)	88% at 10 μM	79% at 10 μM	92% at 10 μM	[1]
Phenmetrazine	29–50.4	70–131	7,765–>10,000	[17][5][18][1]
Naphthylmetrazine (PAL-704)	203	111	RI (105)	[1]
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: [19][20]