Benzofuranylpropylaminopentane

Source: Wikipedia, the free encyclopedia.

For the mode of mechanical ventilation known as BPAP, see
bilevel positive airway pressure
.
BPAP
By mouth[3]
Drug classMonoaminergic activity enhancer
Identifiers
  • (2R)-1-(1-Benzofuran-2-yl)-N-propylpentan-2-amine; (-)-BPAP; BFPAPn; BFPAP
JSmol)
SMILES
  • CCC[C@@H](NCCC)CC1=CC2=C(C=CC=C2)O1
  • InChI=1S/C16H23NO/c1-3-7-14(17-10-4-2)12-15-11-13-8-5-6-9-16(13)18-15/h5-6,8-9,11,14,17H,3-4,7,10,12H2,1-2H3/t14-/m1/s1 checkY
  • Key:LJHIBIVAYHQPBT-CQSZACIVSA-N checkY
  (verify)

(–)-Benzofuranylpropylaminopentane (BPAP; developmental code name FPFS-1169) is an experimental drug related to selegiline which acts as a monoaminergic activity enhancer (MAE).[4][5][6][2] It is orally active in animals.[3]

BPAP is a highly

derivative and tryptamine relative structurally related to phenylpropylaminopentane (PPAP).[5][7][11]

BPAP was first described in 1999.[12][11] There has been interest in BPAP for potential clinical use in humans, including in the treatment of Parkinson's disease, Alzheimer's disease, and depression.[4][12][7] There has also been interest in BPAP to help slow aging.[4][13]

Pharmacology

Pharmacodynamics

Monoaminergic activity enhancer

BPAP is a

catecholaminergic activity enhancer (CAE), BPAP enhances both serotonin and the catecholamines.[11] In addition, BPAP is a more potent MAE than PPAP.[11]

Unlike

psychostimulants like amphetamine, which are monoamine releasing agents that induce release of a flood of monoamine neurotransmitters in an uncontrolled manner, BPAP instead only increases the amount of neurotransmitter that is released when a neuron is stimulated by receiving an impulse from a neighbouring neuron.[3][14] As such, while both amphetamine and BPAP increase the amount of neurotransmitters that are released, amphetamine causes neurons to dump neurotransmitter stores into the synapse regardless of external input, while with BPAP the pattern of neurotransmitter release is not changed.[3][14] Instead, when the neuron would normally release neurotransmitter, a larger amount than normal is released with BPAP.[3][14]

In an

pharmacodynamic activity.[7]

The actions of BPAP and other MAEs are distinct from those of

dopamine receptor agonists bromocriptine and pergolide were all ineffective.[5][12][20]

Recent findings have suggested that known

pre-synaptic nerve terminals.[17]

Other compounds which produce MAE effects are the

picomolar range, and in vivo activity at microgram doses.[4][7][5][6]

BPAP

neurodegeneration, help to preserve behavioral activity with age, and prolong lifespan.[15][6][22][21][13]

Other actions

In addition to its MAE actions, BPAP is a

amphetamines.[5][11] It has been said that the monoamine reuptake inhibition of BPAP is not of pharmacological significance at the much lower concentrations that have MAE activity.[4]

While selegiline is a potent

clorgyline in terms of MAO-A inhibition.[11] The weak MAO-A inhibition of BPAP is said to be without pharmacological significance.[4][11] BPAP has relatively weak affinity for the α2-adrenergic receptor.[4][11] However, this occurs at concentrations well below its MAE actions.[11] The drug is also a weak agonist of the sigma receptor likewise at high concentrations.[7][19][23][24]

Pharmacokinetics

The

elimination half-life was 5.5 to 5.8 hours.[3] The drug is recovered more than 90% in urine and feces 72 hours after administration.[3]

Chemistry

BPAP (1-(benzofuran-2-yl)-2-propylaminopentane) is a

structural modification of phenylpropylaminopentane (PPAP).[5][7][11] It was developed by replacement of the benzene ring in PPAP with a benzofuran ring.[11][25]

The compound is generally studied and used as the R(–)-enantiomer, R(–)-BPAP or simply (–)-BPAP (FPFS-1169).[5][4][11][26][2] This enantiomer is more potent than the S(+)-enantiomer (FPFS-1170).[17][14][2]

Indolylpropylaminopentane (IPAP), an analogue of BPAP, is a MAE for serotonin, norepinephrine, and dopamine that was derived from tryptamine.[15][17][25] Unlike BPAP, it shows some selectivity for serotonin, with its maximal impact on this neurotransmitter occurring at 10-fold lower concentrations than for norepinephrine or dopamine.[17][25]

A derivative of BPAP, 3-F-BPAP, has weak MAE activity and has been found to antagonize the MAE actions of BPAP.[7][27] These findings suggest that 3-F-BPAP interacts with the same receptor or biological target as BPAP and acts as a MAE antagonist.[7][27]

Enantioselective synthesis of (–)-BPAP has been described.[14]

History

BPAP was first described in the

structural modification of phenylpropylaminopentane (PPAP).[4][11][25] It was discovered by the developers of selegiline, including József Knoll and colleagues like Ildikó Miklya.[6][11] PPAP had previously been derived by modification of selegiline.[6][28]

Research

BPAP has been studied in

clinical development for use in humans.[4][3] An effective dosage of BPAP of 0.1 mg/day, one-tenth of that of the less-potent compound selegiline (1 mg/day), has been suggested for study and use in humans.[4][7]

See also

References

  1. ^ "R-(-)-BPAP". CAS Common Chemistry. Chemical Abstract Service, American Chemical Society. 12 August 2024. 260550-89-8. Retrieved 12 August 2024.
  2. ^
    PMID 15102525
    . Among catecholaminergic-serotonergic enhancers, (–)-1-phenyl-2-propylaminopentane [(–)-PPAP] and R-(–)-(benzofuran-2-yl)-2-propylaminopentane [R-(–)-BPAP, the development number; FPFS-1169] are the most promising agents (Knoll et al., 1999). [...] Fig. 1. Chemical structure and abbreviations of used BPAP derivatives. FPFS-1169 and FPFS-1170: R-(–)- and S-(+)-1-(benzofuran-2-yl)-2-propylamino-pentane hydrochloride, [...]
  3. ^
    PMID 12365195
    .
  4. ^
    PMID 11607046
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  5. ^
    S2CID 37564231
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  6. ^
    PMID 27480491
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  7. ^
    PMID 12834268
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  8. ^
    PMID 14659999
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  9. ^
    PMID 11516435
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  10. ^
    PMID 12527038
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  11. ^
    PMID 10588928
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  12. ^
    S2CID 26570703
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  13. ^
    PMID 27777099
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  14. ^
    PMID 11377179
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  15. ^
    ISBN 978-3-540-23969-7
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  16. ^
    PMID 37686140
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  17. ^
    PMID 35955676
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  18. PMID 12175892
    .
  19. ^
    PMID 12204771
    . It is obvious that the bell-shape dose-response curve in the nanomolecular range is responsible for the highly specific enhancer effect of the compound. In contrast, the dose-response curve in the macromolecular range has probably nothing to do with the enhancer regulation and is therefore of lower physiological significance. Recent studies revealed that in this macromolecular dose range (–)-BPAP binds to sigma receptors [2,11].
  20. ^
    PMID 12697274
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  21. ^
    PMID 7869839
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  22. PMID 9498233
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  23. ^ Rashid MH, Matsumoto T, Mizuno K, Watanabe M, Sato N, Yoneda F, et al. "Nociceptive Responses by Deprenyl Derivative, (–)BPAP through Metabotropic Sigma Receptor". Pharmacology Reviews and Communications. 11 (4): 335–342.
  24. PMID 11100977
    .
  25. ^
    PMID 11377178
    .
  26. ^ US 6214859, Yoneda F, Knoll J, Ode H, Sakae H, Katurada M, Moto T, Ando T, Shimazu S, Takahata K, Fujimoto M, "Ethylamine derivatives", issued 10 April 2001, assigned to Fujimoto Brothers Co Ltd. 
  27. ^
    PMID 12175892
    .
  28. PMID 1356324
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  29. PMID 18243357
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  30. PMID 19883738
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