4-PhPr-3,5-DMA

4-PhPr-3,5-DMA, also known as 4-(3-phenylpropyl)-3,5-dimethoxyamphetamine, is a serotonin receptor modulator of the phenethylamine and amphetamine families.^[1] It is structurally related to the DOx drugs but has one of its methoxy groups in the 3 position instead of 2 position on the phenyl ring and has a bulky substitution at the 4 position of the phenyl ring.^[1]

Other names4-(3-Phenylpropyl)-3,5-dimethoxyamphetamine; 1-[3,5-Dimethoxy-4-(3-phenylpropyl)phenyl]-2-aminopropane; 4-PP-3,5-DMA

Drug classSerotonin 5-HT₂ receptor modulator; Serotonin 5-HT_2A receptor partial agonist

CAS Number

• 785765-10-8

PubChem CID

• 10064187

Quick facts Clinical data, Other names ...

4-PhPr-3,5-DMA

Clinical data
Other names	4-(3-Phenylpropyl)-3,5-dimethoxyamphetamine; 1-[3,5-Dimethoxy-4-(3-phenylpropyl)phenyl]-2-aminopropane; 4-PP-3,5-DMA
Drug class	Serotonin 5-HT2 receptor modulator; Serotonin 5-HT2A receptor partial agonist
Identifiers
IUPAC name 1-[3,5-dimethoxy-4-(3-phenylpropyl)phenyl]propan-2-amine
CAS Number	785765-10-8
PubChem CID	10064187
ChemSpider	8239727
ChEMBL	ChEMBL102268
Chemical and physical data
Formula	C20H27NO2
Molar mass	313.441 g·mol−1
3D model (JSmol)	Interactive image
SMILES CC(CC1=CC(=C(C(=C1)OC)CCCC2=CC=CC=C2)OC)N
InChI InChI=1S/C20H27NO2/c1-15(21)12-17-13-19(22-2)18(20(14-17)23-3)11-7-10-16-8-5-4-6-9-16/h4-6,8-9,13-15H,7,10-12,21H2,1-3H3 Key:ATJLAXPLVFCXTQ-UHFFFAOYSA-N

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The affinities (K_i) of 4-PhPr-3,5-DMA for the serotonin 5-HT₂ receptors have been reported to be 4 nM for the serotonin 5-HT_2A receptor and 40 nM for the serotonin 5-HT_2C receptor, with approximately 10-fold selectivity for the serotonin 5-HT_2A receptor over the serotonin 5-HT_2C receptor.^[1] Its affinities for the serotonin 5-HT_2A and 5-HT_2C receptors in the study were approximately 8-fold and 1.6-fold higher than those of DOB, respectively.^[1] The drug was a full agonist of the serotonin 5-HT_2A receptor in terms of phosphatidylinositol (PI) hydrolysis (E_maxTooltip half-maximal effective concentration = 109% relative to serotonin).^[1] However, in the presence of the serotonin 5-HT_2A receptor silent antagonist ketanserin, which should have abolished stimulation, 4-PhPr-3,5-DMA still produced 43% activation of PI hydrolysis.^[1] These findings suggest that 4-PhPr-3,5-DMA may be acting in the assay via a combination of both serotonin 5-HT_2A receptor partial agonism and another unknown ketanserin-insensitive mechanism.^[1]

The observed serotonin 5-HT_2A receptor agonist activity of 4-PhPr-3,5-DMA was surprising, as previously studied DOx derivatives with bulky 4-position substituents such as DOHx had consistently acted as antagonists of the serotonin 5-HT_2A receptor.^[1] In addition, the 3,5-dimethoxy substitution pattern being optimal in the study was unexpected, as the 2,5-dimethoxy pattern has been found to be optimal in the DOx drugs.^[1] The study's findings suggest that bulky substitutions at the 4 position of DOx-like amphetamines can provide enhanced serotonin 5-HT_2A receptor affinity but will not inevitably result in antagonism.^[1] Instead, agonism, and possible psychedelic effects, may be retainable with specific substitution patterns.^[1]

An analogue is 4-PhPr-2,5-DMA (DOPP or DOPhPr), which is also a weak partial agonist of the serotonin 5-HT_2A receptor.^[2][3][4][1]