Phenylpropylaminopentane

Phenylpropylaminopentane
Clinical data
Other namesPPAP; (–)-PPAP; (2R)-PPAP; MK-306; α,N-Dipropylphenethylamine; α-Desmethyl-α,N-dipropylamphetamine; 1-Phenyl-2-propylaminopentane; 1-Phenyl-2-propylamino-pentane; 1-Phenyl-2-propyl-aminopentane
Drug classCatecholaminergic activity enhancer
Legal status
Legal status
Identifiers
  • (2R)-1-Phenyl-N-propylpentan-2-amine
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC14H23N
Molar mass205.345 g·mol−1
3D model (JSmol)
  • CCCN[C@H](CCC)Cc1ccccc1
  • InChI=1S/C14H23N/c1-3-8-14(15-11-4-2)12-13-9-6-5-7-10-13/h5-7,9-10,14-15H,3-4,8,11-12H2,1-2H3/t14-/m1/s1
  • Key:PBENSVGEGPJNFJ-CQSZACIVSA-N

1-Phenyl-2-propylaminopentane (PPAP; developmental code name MK-306) is an experimental drug related to selegiline which acts as a catecholaminergic activity enhancer (CAE).[1][2][3][4]

PPAP is a CAE and enhances the nerve impulse propagation-mediated release of norepinephrine and dopamine.[1][3][4][5] It produces psychostimulant-like effects in animals.[4] The drug is a phenethylamine and amphetamine derivative and was derived from selegiline.[3][4]

PPAP was first described in the literature in 1988[6] and in the first major paper in 1992.[4][7] It led to the development of the improved monoaminergic activity enhancer (MAE) benzofuranylpropylaminopentane (BPAP) in 1999.[1][3] PPAP was a reference compound for studying the MAE system for many years.[1][2][3] However, it was superseded by BPAP, which is more potent, selective, and also enhances serotonin.[8][1][2][3][9][10] There has been interest in PPAP for potential clinical use in humans,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.[4]

  1. ^ a b c d e Knoll J (2001). "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. 7 (3): 317–45. doi:10.1111/j.1527-3458.2001.tb00202.x. PMC 6494119. PMID 11607046. Recognizing that (–)deprenyl-induced activation of the nigrostriatal dopaminergic system is unrelated to the inhibition of MAO-B (32), we performed a structure-activity relationship study with the aim of developing deprenyl analogues that, on the one hand, are free of the MAO inhibitory property and, on the other hand, are, in contrast to deprenyl, not metabolized to amphetamines (44). (–)PPAP was selected as a reference substance for further studies. Although (–)PPAP was the first PEA-derived enhancer substance free of the unwanted effects of (–)deprenyl, its clinical efficiency was, in spite of all our efforts, never tested. Figure 8 shows the chemical structure and pharmacologic spectrum of the most important PEA-derived substances that have an enhancer effect.
  2. ^ a b c Knoll J (August 2003). "Enhancer regulation/endogenous and synthetic enhancer compounds: a neurochemical concept of the innate and acquired drives". Neurochem Res. 28 (8): 1275–1297. doi:10.1023/a:1024224311289. PMID 12834268. Because (–)-deprenyl is a highly potent and selective inhibitor of MAO-B, we performed a structure–activity relationship study to develop a deprenyl-derived enhancer substance free of the MAO-B inhibitory property (11). (–)-1-Phenyl-2-propylaminopentane [(–)-PPAP] is our reference substance with this pharmacological profile. [...] Remarkably, 1 mg/kg (–)-PPAP, a (–)-deprenyl–derived enhancer substance devoid of the MAO-B inhibitory potency of its parent compound, fully antagonized tetrabenazine-induced learning depression in HP rats and was ineffective in LP rats. [...] Furthermore, 3-F-BPAP did not influence the enhancer effect of (–)-PPAP, a (–)-deprenyl analogue free of MAO-B inhibitory potency (34, Fig. 4). The data clearly show that the molecular mechanism through which the PEA-derived substances, (–)-deprenyl and (–)-PPAP, exert their enhancer effect in vivo, is not identical with the one through the stimulation of which the tryptamine-derived substance, (–)-BPAP, acts.
  3. ^ a b c d e f Gaszner P, Miklya I (January 2006). "Major depression and the synthetic enhancer substances, (-)-deprenyl and R-(-)-1-(benzofuran-2-yl)-2-propylaminopentane". Progress in Neuro-Psychopharmacology & Biological Psychiatry. 30 (1): 5–14. doi:10.1016/j.pnpbp.2005.06.004. PMID 16023777. S2CID 26570703. This was shown with the development of (–)-1-phenyl-2-propylaminopentane, (–)-PPAP, a derivative of (–)-deprenyl which shared the enhancer activity with its parent compound but was free of its MAO-B inhibitory property (Knoll et al., 1992). (–)-PPAP enhanced dopaminergic activity in the brain like (–)-deprenyl. Knoll's progress in clarifying the mechanism of action of (–)-deprenyl responsible for enhanced dopaminergic activity can be followed in his sequent reviews (Knoll, 1978, 1983, 1987, 1992, 1995), until he came to the final conclusion that (–)-deprenyl acts primarily as a PEA-derived synthetic enhancer substance (Knoll, 1998). [...] Since (–)-deprenyl is a highly potent and selective inhibitor of MAO-B, a structure –activity relationship study was performed to develop a deprenyl-derived enhancer substance being free of the MAO-B inhibitory property (Knoll et al., 1992), and (–)-PPAP is at present the reference substance with this pharmacological profile. [...] The subcutaneous administration of 1 mg/kg tetrabenazine, once daily for 5 days, which depletes the catecholamine stores in the brain, significantly inhibits in rats the acquisition of a two-way conditioned avoidance reflex in the shuttle box. Enhancer substances antagonize, in a dose-dependent manner, the inhibition of learning caused by tetrabenazine. The tryptamine-derived selective and highly potent enhancer, BPAP acted in dose range from 0.05 to 10 mg/kg. The PEA-derived enhancer substances, (–)-deprenyl and (–)-PPAP were much less active (1–5 mg/kg).
  4. ^ a b c d e f Knoll J, Knoll B, Török Z, Timár J, Yasar S (1992). "The pharmacology of 1-phenyl-2-propylamino-pentane (PPAP), a deprenyl-derived new spectrum psychostimulant". Archives Internationales de Pharmacodynamie et de Therapie. 316: 5–29. PMID 1356324.
  5. ^ Cite error: The named reference KnollMiklyaKnoll1996 was invoked but never defined (see the help page).
  6. ^ Cite error: The named reference KnollTimarKnoll1988 was invoked but never defined (see the help page).
  7. ^ Cite error: The named reference Healy2000 was invoked but never defined (see the help page).
  8. ^ Cite error: The named reference Miklya2016 was invoked but never defined (see the help page).
  9. ^ Cite error: The named reference ShimazuMiklya2004 was invoked but never defined (see the help page).
  10. ^ Cite error: The named reference KnollYonedaKnoll1999 was invoked but never defined (see the help page).