Di-β-phenylisopropylamine

Di-β-phenylisopropylamine
Clinical data
Drug class	Central nervous system stimulant; Serotonin 5-HT1A receptor agonist; norepinephrine reuptake inhibitor; serotonin reuptake inhibitor; adrenergic agonist; prodrug
ATC code	none;
Pharmacokinetic data
Metabolites	amphetamine
Identifiers
CAS Number	10509-86-1;
PubChem CID	99869;
ChemSpider	90234;
UNII	HNZ7L49KE6;
CompTox Dashboard (EPA)	DTXSID00909322;
Chemical and physical data
Formula	C18H23N
Molar mass	253.389 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC(CC1=CC=CC=C1)NC(C)CC2=CC=CC=C2;
	InChI InChI=1S/C18H23N/c1-15(13-17-9-5-3-6-10-17)19-16(2)14-18-11-7-4-8-12-18/h3-12,15-16,19H,13-14H2,1-2H3; Key:XIZFJFZATSHCAL-UHFFFAOYSA-N;

di-β-phenylisopropylamine also known by the abbreviations DPIA or DPEA, or N,N-Di-β-phenylisopropylamine, and also under the code name Iem-1365, it is a central nervous system stimulant but, above all, a serotonergic agent that also exhibits adrenergic activity; it has been shown to cause central nervous system effects and toxicity similar to those of amphetamine.^[2]

DPIA is a secondary amine; structurally, the molecule can be described as comprising a single central amine, to which two isopropyl chains with benzene rings at their ends are attached symmetrically on either side.

Pharmacology

Pharmacodynamics

DPIA is a norepinephrine transporter inhibitor with an IC₅₀ value of 3.1 µM, as well as a dopamine transporter inhibitor with a potency approximately 13 times weaker than that of amphetamine, but 7 times more potent than amphetamine in inhibiting the serotonin transporter, although, unlike amphetamine, DPIA does not exhibit monoamine-releasing activity. It exhibits moderate affinity for 5-HT_1A serotonin receptors (K_i = 3.5 µM) and for alpha-1A-adrenoreceptors (K_i = 0.12 µM), and binds to alpha-2A-adrenoreceptors and TAAR1.^[2]

In experiments on rodents, DPIA produced the same central effects and toxicity as amphetamine, but was less potent. Interestingly, unlike amphetamine, DPIA caused a reduction in heart rate and blood pressure (exhibiting cardiodepressant properties).^[2]^[3]

Pharmacokinetics

It is thought that the main metabolic pathway for DPIA is its conversion to amphetamine.^[1]

References

1 2 Ottaviano V, Furnari C, Rosati F (2002). "Identification of di(beta-phenylisopropyl)amine as the main ingredient in illicit amphetamine tablets". Annali dell'Istituto Superiore di Sanita. 38 (3): 331–335. PMID 12645186.
1 2 3 Kolaczynska KE, Ducret P, Trachsel D, Hoener MC, Liechti ME, Luethi D (June 2022). "Pharmacological characterization of 3,4-methylenedioxyamphetamine (MDA) analogs and two amphetamine-based compounds: N,α-DEPEA and DPIA". European Neuropsychopharmacology. 59: 9–22. doi:10.1016/j.euroneuro.2022.03.006. PMID 35378384.
↑ Ketema H, Davis WM, Walker LA, Borne RF (1990). "Pharmacologic and toxicologic effects of di(beta-phenylisopropyl)amine (DPIA) in rats and mice". General Pharmacology. 21 (5): 783–790. doi:10.1016/0306-3623(90)91034-o. PMID 2276597.

[Ottaviano_2002-1] 1 2 Ottaviano V, Furnari C, Rosati F (2002). "Identification of di(beta-phenylisopropyl)amine as the main ingredient in illicit amphetamine tablets". Annali dell'Istituto Superiore di Sanita. 38 (3): 331–335. PMID 12645186.

[Kolaczynska_2022-2] 1 2 3 Kolaczynska KE, Ducret P, Trachsel D, Hoener MC, Liechti ME, Luethi D (June 2022). "Pharmacological characterization of 3,4-methylenedioxyamphetamine (MDA) analogs and two amphetamine-based compounds: N,α-DEPEA and DPIA". European Neuropsychopharmacology. 59: 9–22. doi:10.1016/j.euroneuro.2022.03.006. PMID 35378384.

[3] Ketema H, Davis WM, Walker LA, Borne RF (1990). "Pharmacologic and toxicologic effects of di(beta-phenylisopropyl)amine (DPIA) in rats and mice". General Pharmacology. 21 (5): 783–790. doi:10.1016/0306-3623(90)91034-o. PMID 2276597.

[1]

[2]

[3]