Pseudophenmetrazine

Pseudophenmetrazine is a psychostimulant of the phenylmorpholine group. It is the N-demethylated and cis-configured analogue of phendimetrazine as well as the cis-configured stereoisomer of phenmetrazine.^[1] In addition, along with phenmetrazine, it is believed to be one of the active metabolites of phendimetrazine, which itself is inactive and behaves merely as a prodrug.^[2]

Pseudophenmetrazine

Clinical data
ATC code	None
Identifiers
IUPAC name (±)-cis-3-methyl-2-phenylmorpholine or (±)-(2RS,3SR)-3-methyl-2-phenylmorpholine
CAS Number	13580-23-9 Y
PubChem CID	10329865
ChemSpider	8505326
UNII	5BXE22Z857
Chemical and physical data
Formula	C11H15NO
Molar mass	177.247 g·mol−1
3D model (JSmol)	Interactive image
SMILES C[C@@H]1[C@@H](OCCN1)C2=CC=CC=C2
InChI InChI=1S/C11H15NO/c1-9-11(13-8-7-12-9)10-5-3-2-4-6-10/h2-6,9,11-12H,7-8H2,1H3/t9-,11-/m1/s1 Key:OOBHFESNSZDWIU-MWLCHTKSSA-N

Relative to phenmetrazine, pseudophenmetrazine is of fairly low potency, acting as a modest releasing agent of norepinephrine (EC₅₀ = 514 nM), while its (+)-enantiomer is a weak releaser of dopamine (EC₅₀ = 1,457 nM) whereas its (−)-enantiomer is a weak reuptake inhibitor of dopamine (K_i = 2,691 nM);^[2][3] together as a racemic mixture with the two enantiomers combined, pseudophenmetrazine behaves overall more as a dopamine reuptake inhibitor (K_i = 2,630 nM),^[2][3] possibly due to the (+)-enantiomer blocking the uptake of the (−)-enantiomer into dopaminergic neurons and thus preventing it from inducing dopamine release. Neither enantiomer has any significant effect on serotonin reuptake or release (both K_i = >10,000 nM and EC₅₀ = >10,000 nM, respectively).^[2][3]

Monoamine release of pseudophenmetrazine and related agents (EC₅₀Tooltip Half maximal effective concentration, nM)

Compound	NETooltip Norepinephrine	DATooltip Dopamine	5-HTTooltip Serotonin	Ref
Phenethylamine	10.9	39.5	>10,000	[4][5][6]
Dextroamphetamine	6.6–10.2	5.8–24.8	698–1,765	[7][8][6][9]
Dextromethamphetamine	12.3–14.3	8.5–40.4	736–1,292	[7][10][6][9]
2-Phenylmorpholine	79	86	20,260	[11]
Phenmetrazine	29–50.4	70–131	7,765–>10,000	[12][6][13][11]
(+)-Phenmetrazine	37.5	87.4	3246	[12]
(–)-Phenmetrazine	62.9	415	>10,000	[12]
Phendimetrazine	>10,000	>10,000	>100,000	[12][6][9]
Pseudophenmetrazine	514	>10,000 (RI)	>10,000	[12]
(+)-Pseudophenmetrazine	349	1,457	>10,000	[12]
(–)-Pseudophenmetrazine	2,511	IA (RI)	>10,000	[12]
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. Refs: [14][15]