 | |
| Clinical data | |
|---|---|
| Other names | PAL-678; PAL678; 2-(2′-Naphthyl)morpholine; 2-(Naphthalen-2-yl)morpholine |
| Drug class | Monoamine releasing agent |
| Identifiers | |
| |
| CAS Number | |
| PubChemCID | |
| ChemSpider | |
| Chemical and physical data | |
| Formula | C14H15NO |
| Molar mass | 213.280 g·mol−1 |
| 3D model (JSmol) | |
| |
| |
Naphthylmorpholine (code namePAL-678), also known as2-(2′-naphthyl)morpholine, is amonoamine releasing agent of thearylmorpholine andnaphthylethylamine families.[1][2] It is thederivative of2-phenylmorpholine with a 2-naphthalenering instead of aphenyl ring.[1][2] Naphthylmorpholine is a closeanalogue ofnaphthylmetrazine (PAL-704; a naphthalene analogue ofphenmetrazine), but lacks naphthylmetrazine'smethyl group at the 3 position of themorpholine ring.[1][2]
The drug is apotent monoamine releasing agent.[1] ItsEC50Tooltip half-maximal effective concentration values for induction of monoamine release have not been reported, but it released 92% ofserotonin, 88% ofnorepinephrine, and 79% ofdopamine at a concentration of 10,000 nM in rat brainsynaptosomes.[1] Hence, it appears to act preferentially as a releaser of serotonin and norepinephrine and to a lesser extent of dopamine.[1]
| 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 | 46a | 12a | [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. Theassays were done in rat brainsynaptosomes and humanpotencies may be different. See alsoMonoamine releasing agent § Activity profiles for a larger table with more compounds.Footnotes:aENAPTooltip Ethylnaphthylaminopropane is apartial releaser of serotonin (EmaxTooltip maximal efficacy = 66%) and dopamine (Emax = 78%).Refs:[19][20] | ||||
3-Methyl-2-(2′-Naphthyl)morpholine hydrochloride (4c, PAL 704) [...] Two of the compounds, PAL-704 and PAL-788, show unique and interesting hybrid activity in that they are DA/NE releasers, but are 5HT uptake inhibitors. [...] TABLE 4 Comparison of the DA, 5-HT, and NE Releasing Activity of a Series of Phenmetrazine Analogs [...]
RESULTS. Methamphetamine and amphetamine potently released NE (IC50s = 14.3 and 7.0 nM) and DA (IC50s = 40.4 nM and 24.8 nM), and were much less potent releasers of 5-HT (IC50s = 740 nM and 1765 nM). Phentermine released all three biogenic amines with an order of potency NE (IC50 = 28.8 nM)> DA (IC50 = 262 nM)> 5-HT (IC50 = 2575 nM). Aminorex released NE (IC50 = 26.4 nM), DA (IC50 = 44.8 nM) and 5-HT (IC50 = 193 nM). Chlorphentermine was a very potent 5-HT releaser (IC50 = 18.2 nM), a weaker DA releaser (IC50 = 935 nM) and inactive in the NE release assay. Chlorphentermine was a moderate potency inhibitor of [3H]NE uptake (Ki = 451 nM). Diethylpropion, which is self-administered, was a weak DA uptake inhibitor (Ki = 15 µM) and NE uptake inhibitor (Ki = 18.1 µM) and essentially inactive in the other assays. Phendimetrazine, which is self-administered, was a weak DA uptake inhibitor (IC50 = 19 µM), a weak NE uptake inhibitor (8.3 µM) and essentially inactive in the other assays.
FIGURE 2-6: Release: Effects of the specified test drug on monoamine release by DAT (red circles), NET (blue squares), and SERT (black traingles) in rat brain tissue. [...] EC50 values determined for the drug indicated within the panel. [...]