Phenylpropylaminopentane

Overview

1-Phenyl-2-propylaminopentane (PPAP), also known as α,N-dipropylphenethylamine (DPPEA) and by the developmental code name MK-306, is an experimental drug related to selegiline which acts as a catecholaminergic activity enhancer (CAE).[1–4] WP

PPAP is a CAE and enhances the nerve impulse propagation-mediated release of norepinephrine and dopamine. It produces psychostimulant-like effects in animals. In 2025, it was discovered that PPAP is a potent catecholamine reuptake inhibitor, including of dopamine and to a lesser extent of norepinephrine. The drug is a phenethylamine and amphetamine derivative and was derived via structural modification of selegiline.[1][3–6] WP

PPAP was first described in the literature in 1988 and in the first major paper in 1992. It led to the development of the improved monoaminergic activity enhancer (MAE) benzofuranylpropylaminopentane (BPAP) in 1999. PPAP was a reference compound for studying the MAE system for many years. However, it was superseded by BPAP, which is more potent, selective, and also enhances serotonin. There has been interest in PPAP for potential clinical use in humans, including in the treatment of depression, attention deficit hyperactivity disorder (ADHD), and Alzheimer's disease. It is a controlled substance in Sweden as of 2020.[1–4][7–12] WP

Drug class

Catecholaminergic activity enhancer Norepinephrine–dopamine reuptake inhibitor Stimulant WP

From the Wikipedia article's infobox.

Pharmacology

Catecholaminergic activity enhancer

PPAP is classified as a catecholaminergic activity enhancer (CAE), a drug that stimulates the impulse propagation-mediated release of the catecholamine neurotransmitters norepinephrine and dopamine in the brain.[1–5][13] WP

Unlike stimulants such as amphetamine, which release a flood of monoamine neurotransmitters in an uncontrolled manner, (–)-PPAP instead only increases the amount of neurotransmitters that get released when a neuron is stimulated by receiving an impulse from a neighboring neuron. Both amphetamine and (–)-PPAP promote the release of monoamines; however, while amphetamine causes neurons to release neurotransmitter stores into the synapse regardless of external input, (–)-PPAP does not influence the pattern of neurotransmitter release and instead releases a larger amount of neurotransmitters than normal.[5][13] WP

Findings in the early 2020s have suggested that known synthetic monoaminergic activity enhancers (MAEs) like PPAP, BPAP, and selegiline may exert their effects via trace amine-associated receptor 1 (TAAR1) agonism. This was evidenced by the TAAR1 antagonist EPPTB reversing the MAE effects of BPAP and selegiline, among other findings. Another compound, rasagiline, has likewise been found to reverse the effects of MAEs, and has been proposed as a possible TAAR1 antagonist.[14][15] WP

The therapeutic index for PPAP in animal models is greater than that of amphetamine while producing comparable improvements in learning, retention, and antidepressant effects. It has been found to reduce deficits induced by the dopamine depleting agent tetrabenazine in the shuttle box learning test in rats.[4][16] WP

PPAP and selegiline are much less potent than BPAP as MAEs. Whereas PPAP and selegiline are active at doses of 1 to 5 mg/kg in vivo in rats, BPAP is active at doses of 0.05 to 10 mg/kg. BPAP is 130 times as potent as selegiline in the shuttle box test. In contrast to BPAP however, the MAE effects of PPAP and selegiline are not reversed by the BPAP antagonist 3-F-BPAP. In addition, whereas PPAP and selegiline are selective as MAEs of norepinephrine and dopamine, BPAP is a MAE of not only norepinephrine and dopamine but also of serotonin.[1–4][11] WP

Catecholamine reuptake inhibitor

PPAP was reported in 2025 to act as a potent catecholamine reuptake inhibitor, with IC₅₀ (half-maximal inhibitory concentration) values of 57.5 nM at the dopamine transporter (DAT), 571 nM at the norepinephrine transporter (NET), and 19,000 nM at the serotonin transporter (SERT). In terms of dopamine reuptake inhibition, it was 41-fold less potent than MDPV but 7-fold more potent than mephedrone (4-MMC) and 1.3-fold more potent than amphetamine.[6] WP

Other actions

Unlike the related CAE selegiline, (–)-PPAP has no activity as a monoamine oxidase inhibitor.[9][17] WP

Research

Research

PPAP has been proposed as a potential therapeutic agent for attention deficit hyperactivity disorder (ADHD), Alzheimer's disease, and depression based on preclinical findings. The developers of PPAP attempted to have it clinically studied, but were unsuccessful and it was never assessed in humans.[1][4] WP

History

History

Racemic PPAP (MK-306) was first described in the scientific literature in 1988 and a series of papers characterizing it were published in the early 1990s. The first major paper on the drug was published in 1992. It was synthesized by József Knoll and colleagues. The potencies of the different enantiomers of PPAP were assessed in 1994. Subsequent papers have employed (–)-PPAP.[1][2][4][5][7][8][16][18–25] WP

Several patents of PPAP have been published.[26][27][28] WP

The development of PPAP was critical in elucidating that the CAE effects of selegiline are unrelated to its monoamine oxidase inhibition. For many years, PPAP served as a reference compound in studying MAEs. However, it was eventually superseded by BPAP, which was discovered in 1999. This MAE is more potent and selective than PPAP and, in contrast to PPAP and selegiline, also enhances serotonin.[1][2][3][9][10][11] WP

In 2025, PPAP was found to act as a potent catecholamine reuptake inhibitor.[6] WP

Legal status

Sweden

PPAP is a controlled substance in Sweden as of 2020.[12] WP

Chemistry

Formula

C14H23N PC

CAS number

784118-64-5 PC

Molar mass (g/mol)

205.34 PC

IUPAC name (computed by PubChem)

(2R)-1-phenyl-N-propylpentan-2-amine PC

SMILES

CCC[C@H](CC1=CC=CC=C1)NCCC PC

InChIKey

PBENSVGEGPJNFJ-CQSZACIVSA-N PC

PubChem CID

51529346

IUPAC name

(2R)-1-Phenyl-N-propylpentan-2-amine WP

Mixing

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Journal / agency Knoll J. Antiaging compounds: (-)deprenyl (selegeline) and (-)1-(benzofuran-2-yl)-2-propylaminopentane, [(-)BPAP], a selective highly potent enhancer of the impulse propagation mediated release of catecholamine and serotonin in the brain. CNS Drug Rev. 2001. doi:10.1111/j.1527-3458.2001.tb00202.x · PMID 11607046 · PMC6494119
2. Journal / agency Knoll J. Enhancer regulation/endogenous and synthetic enhancer compounds: a neurochemical concept of the innate and acquired drives. Neurochem Res. August 2003. doi:10.1023/a:1024224311289 · PMID 12834268
3. Journal / agency Gaszner P, Miklya I. Major depression and the synthetic enhancer substances, (-)-deprenyl and R-(-)-1-(benzofuran-2-yl)-2-propylaminopentane. Progress in Neuro-Psychopharmacology & Biological Psychiatry. January 2006. doi:10.1016/j.pnpbp.2005.06.004 · PMID 16023777
4. Journal / agency Knoll J, Knoll B, Török Z, Timár J, Yasar S. The pharmacology of 1-phenyl-2-propylamino-pentane (PPAP), a deprenyl-derived new spectrum psychostimulant. Archives Internationales de Pharmacodynamie et de Therapie. 1992. PMID 1356324
5. Journal / agency Knoll J, Miklya I, Knoll B, Markó R, Kelemen K. (-)Deprenyl and (-)1-phenyl-2-propylaminopentane, [(-)PPAP], act primarily as potent stimulants of action potential-transmitter release coupling in the catecholaminergic neurons. Life Sciences. February 1996. doi:10.1016/0024-3205(96)00014-8 · PMID 8602114
6. Journal / agency Stalberga D, Kronstrand R, Schranz B, van Zijl N, Karlman S, Aref S, Rautio T, Vikingsson S, Persson M, Green H. Comprehensive in vitro profiling of traditional and emerging stimulants at monoamine transporters and the 5-HT2A receptor. Br J Pharmacol. July 2026. doi:10.1111/bph.70587 · PMID 42449077
7. Journal / agency Knoll B, Timar J, Knoll J. Amphetamine-derived potent psychostimulants devoid of biogenic amine releasing properties. Pharmacological Research Communications. 1988. doi:10.1016/S0031-6989(88)80670-2
8. Journal / agency Healy D. The Psychopharmacologists, Vol. III: Interviews. 2000. doi:10.4324/9781003058892-3
9. Journal / agency Miklya I. The significance of selegiline/(-)-deprenyl after 50 years in research and therapy (1965-2015). Mol Psychiatry. November 2016. doi:10.1038/mp.2016.127 · PMID 27480491
10. Journal / agency Shimazu S, Miklya I. Pharmacological studies with endogenous enhancer substances: beta-phenylethylamine, tryptamine, and their synthetic derivatives. Prog Neuropsychopharmacol Biol Psychiatry. May 2004. doi:10.1016/j.pnpbp.2003.11.016 · PMID 15093948
11. Journal / agency Knoll J, Yoneda F, Knoll B, Ohde H, Miklya I. (-)1-(Benzofuran-2-yl)-2-propylaminopentane, [(-)BPAP], a selective enhancer of the impulse propagation mediated release of catecholamines and serotonin in the brain. British Journal of Pharmacology. December 1999. doi:10.1038/sj.bjp.0702995 · PMID 10588928 · PMC1571822
12. Other PPAP (Фенилпропиламинопентан)
13. Journal / agency Bandala C, Cárdenas-Rodríguez N, Mendoza-Torreblanca JG, Contreras-García IJ, Martínez-López V, Cruz-Hernández TR, Carro-Rodríguez J, Vargas-Hernández MA, Ignacio-Mejía I, Alfaro-Rodriguez A, Lara-Padilla E. Therapeutic Potential of Dopamine and Related Drugs as Anti-Inflammatories and Antioxidants in Neuronal and Non-Neuronal Pathologies. Pharmaceutics. February 2023. doi:10.3390/pharmaceutics15020693 · PMID 36840015 · PMC9966027
14. Journal / agency Harsing LG, Knoll J, Miklya I. Enhancer Regulation of Dopaminergic Neurochemical Transmission in the Striatum. Int J Mol Sci. August 2022. doi:10.3390/ijms23158543 · PMID 35955676 · PMC9369307
15. Journal / agency Harsing LG, Timar J, Miklya I. Striking Neurochemical and Behavioral Differences in the Mode of Action of Selegiline and Rasagiline. Int J Mol Sci. August 2023. doi:10.3390/ijms241713334 · PMID 37686140 · PMC10487936
16. Journal / agency Gyarmati S, Timár J, Barna L, Knoll B, Knoll J. Reversal of shuttle-box deficit by 1-phenyl-2-propylaminopentane (PPAP). European Neuropsychopharmacology. September 1994. doi:10.1016/0924-977X(94)90109-0
17. Journal / agency Csaba G, Kovács P, Pállinger E. Acute and delayed effect of (-) deprenyl and (-) 1-phenyl-2-propylaminopentane (PPAP) on the serotonin content of peritoneal cells (white blood cells and mast cells). Cell Biochemistry and Function. January–February 2006. doi:10.1002/cbf.1183 · PMID 15584092
18. Journal / agency Knoll B, Yasar S, Timár J, Knoll J. A (-) deprenyl-derived new spectrum psychostimulant. Acta Physiol Hung. 1990. PMID 1973564
19. Journal / agency Yasar S, Timár J, Knoll B, Knoll J. Comparison of the dependence capacity of amphetamine, MK-306 and (-)deprenyl. Acta Physiol Hung. 1990. PMID 2115235
20. Journal / agency Knoll B, Yasar S, Faragó I, Kovács I, Knoll J. 1-phenyl-2-propyl-aminopentane. HCl (MK-306): A deprenyl-derived new spectrum psychostimulant. European Journal of Pharmacology. 1990. doi:10.1016/0014-2999(90)94608-Z
21. Journal / agency Knoll B, Yasar S, Farago I, Kovacs I, Knoll J. 1-phenyl-2-propyl-aminopentane.HCl (MK-306): a deprenyl-derived new spectrum psychostimulant. European Journal of Pharmacology. 1990. doi:10.1016/0014-2999(90)93343-O
22. Journal / agency Timár J, Yasar S, Knoll B, Knoll J. Comparison of the effects of (-)deprenyl, 1-phenyl-2-propyl-aminopentane (MK-306) and amphetamine on the striatal and limbic dopaminergic system. Acta Physiol Hung. 1990. PMID 2115233
23. Journal / agency Gyarmati S, Hársing LG, Tekes K, Knoll J. Repeated administration of (-)deprenyl leaves the mesolimbic dopaminergic activity unchanged. Acta Physiol Hung. 1990. PMID 2115226
24. Journal / agency Knoll B, Timár J, Knoll J. Analysis of the mechanism of the action of the psychostimulant effect of 1-phenyl-2-propylaminopentane (PPAP). A comparison with amphetamine. Pharmacological Research. 1992. doi:10.1016/1043-6618(92)90280-O
25. Journal / agency Simon K, Harmat V, Török Z, Böcskei Z, Hermecz I. 1-Phenyl-2-(propylamino)pentane, a Memory Enhancer. Acta Crystallographica Section C Crystal Structure Communications. 15 August 1996. doi:10.1107/S0108270196005148
26. Other Psychostimulant agent
27. Other Method of treatment of learning deficiency
28. Other Ethylamine derivatives

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