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| Clinical data | |
|---|---|
| Other names | PAL-678; PAL678; 2-(2′-Naphthyl)morpholine; 2-(Naphthalen-2-yl)morpholine |
| Drug class | Monoamine releasing agent |
| Identifiers | |
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| CAS Number | |
| PubChem CID | |
| ChemSpider | |
| Chemical and physical data | |
| Formula | C14H15NO |
| Molar mass | 213.280 g·mol−1 |
| 3D model (JSmol) | |
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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]
The drug is a potent monoamine releasing agent.[1] Its EC50 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]
| Compound | NE | DA | 5-HT | 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 ENAP is a partial releaser of serotonin (Emax = 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. [...]
