3-F-BPAP

Last updated
3-F-BPAP
3-F-BPAP.svg
Clinical data
Other namesTrifluoro-BPAP; Trifluoro-benzofuranylpropylaminopentane
Drug class Monoaminergic activity enhancer antagonist
Identifiers
  • 1-(1-benzofuran-2-yl)-N-(3,3,3-trifluoropropyl)pentan-2-amine
CAS Number
PubChem CID
ChemSpider
Chemical and physical data
Formula C16H20F3NO
Molar mass 299.337 g·mol−1
3D model (JSmol)
  • CCCC(CC1=CC2=CC=CC=C2O1)NCCC(F)(F)F
  • InChI=1S/C16H20F3NO/c1-2-5-13(20-9-8-16(17,18)19)11-14-10-12-6-3-4-7-15(12)21-14/h3-4,6-7,10,13,20H,2,5,8-9,11H2,1H3
  • Key:JCZRCOLYSDAPPW-UHFFFAOYSA-N

3-F-BPAP is a trifluorinated derivative of benzofuranylpropylaminopentane (BPAP) and is an antagonist of the monoaminergic activity enhancer (MAE) effects of the tryptamine-related BPAP. [1] [2] [3] [4] [5]

Conversely, 3-F-BPAP does not antagonize the catecholaminergic activity enhancer (CAE) effects of the phenethylamine-derived selegiline (L-deprenyl) and phenylpropylaminopentane (PPAP). [1] [2] [3] [4] This suggests that different MAEs like BPAP and selegiline may not be identical in their actions and might be acting via different receptor subtypes. [1] [2] [3] [4] [6] [5] In contrast to 3-F-BPAP however, the TAAR1 antagonist EPPTB antagonizes the MAE effects of both BPAP and selegiline. [7] [8]

3-F-BPAP has a weak MAE effect itself but with much lower potency than BPAP. [2] [3] [4] [5] The effects of MAEs like BPAP and selegiline appear to be mediated by TAAR1 agonism, and hence 3-F-BPAP may be acting as a TAAR1 antagonist (or weak partial agonist). [7] [8] [5]

3-F-BPAP was developed by József Knoll and colleagues and was first described in the scientific literature in 2002. [5]

Related Research Articles

<span class="mw-page-title-main">Phenethylamine</span> Organic compound, a stimulant in humans

Phenethylamine (PEA) is an organic compound, natural monoamine alkaloid, and trace amine, which acts as a central nervous system stimulant in humans. In the brain, phenethylamine regulates monoamine neurotransmission by binding to trace amine-associated receptor 1 (TAAR1) and inhibiting vesicular monoamine transporter 2 (VMAT2) in monoamine neurons. To a lesser extent, it also acts as a neurotransmitter in the human central nervous system. In mammals, phenethylamine is produced from the amino acid L-phenylalanine by the enzyme aromatic L-amino acid decarboxylase via enzymatic decarboxylation. In addition to its presence in mammals, phenethylamine is found in many other organisms and foods, such as chocolate, especially after microbial fermentation.

<span class="mw-page-title-main">Tryptamine</span> Metabolite of the amino acid tryptophan

Tryptamine is an indolamine metabolite of the essential amino acid, tryptophan. The chemical structure is defined by an indole—a fused benzene and pyrrole ring, and a 2-aminoethyl group at the second carbon. The structure of tryptamine is a shared feature of certain aminergic neuromodulators including melatonin, serotonin, bufotenin and psychedelic derivatives such as dimethyltryptamine (DMT), psilocybin, psilocin and others.

<span class="mw-page-title-main">Tyramine</span> Chemical compound

Tyramine, also known under several other names, is a naturally occurring trace amine derived from the amino acid tyrosine. Tyramine acts as a catecholamine releasing agent. Notably, it is unable to cross the blood-brain barrier, resulting in only non-psychoactive peripheral sympathomimetic effects following ingestion. A hypertensive crisis can result, however, from ingestion of tyramine-rich foods in conjunction with the use of monoamine oxidase inhibitors (MAOIs).

<span class="mw-page-title-main">Selegiline</span> Monoamine oxidase inhibitor

Selegiline, also known as L-deprenyl and sold under the brand names Eldepryl, Zelapar, and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. It has also been studied and used off-label for a variety of other indications, but has not been formally approved for any other use. The medication, in the form licensed for depression, has modest effectiveness for this condition that is similar to that of other antidepressants. Selegiline is provided as a swallowed tablet or capsule or an orally disintegrating tablet (ODT) for Parkinson's disease and as a patch applied to skin for depression.

<span class="mw-page-title-main">Deprenyl</span> Pharmaceutical drug

Deprenyl, also known by its developmental code name E-250 and as N-propargylmethamphetamine, is the racemic mixture of D-deprenyl and L-deprenyl (selegiline). It was discovered in 1961 in Hungary at Chinoin Pharmaceutical Company by Zoltan Ecseri and József Knoll, was patented in 1962, and was first described in the literature in 1964 or 1965.

<span class="mw-page-title-main">Dopaminergic</span> Substance related to dopamine functions

Dopaminergic means "related to dopamine", a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain.

<span class="mw-page-title-main">Levmetamfetamine</span> Topical nasal decongestant

Levmetamfetamine, also known as l-desoxyephedrine or levomethamphetamine, and commonly sold under the brand name Vicks VapoInhaler among others, is an optical isomer of methamphetamine primarily used as a topical nasal decongestant. It is used to treat nasal congestion from allergies and the common cold. It was first used medically as decongestant beginning in 1958 and has been used for such purposes, primarily in the United States, since then.

<span class="mw-page-title-main">Clorgiline</span> Chemical compound

Clorgiline (INN), or clorgyline (BAN), is a monoamine oxidase inhibitor (MAOI) structurally related to pargyline which is described as an antidepressant. Specifically, it is an irreversible and selective inhibitor of monoamine oxidase A (MAO-A). Clorgiline was never marketed, but it has found use in scientific research. It has been found to bind with high affinity to the σ1 receptor (Ki = 3.2 nM) and with very high affinity to the I2 imidazoline receptor (Ki = 40 pM).

<span class="mw-page-title-main">Rasagiline</span> Chemical compound

Rasagiline, sold under the brand name Azilect among others, is a medication which is used in the treatment of Parkinson's disease. It is used as a monotherapy to treat symptoms in early Parkinson's disease or as an adjunct therapy in more advanced cases. The drug is taken by mouth.

<span class="mw-page-title-main">Benzofuranylpropylaminopentane</span> Chemical compound

(–)-Benzofuranylpropylaminopentane is an experimental drug related to selegiline which acts as a monoaminergic activity enhancer (MAE). It is orally active in animals.

<span class="mw-page-title-main">Phenylpropylaminopentane</span> Stimulant drug of the substituted phenethylamine class

1-Phenyl-2-propylaminopentane is an experimental drug related to selegiline which acts as a catecholaminergic activity enhancer (CAE).

<span class="mw-page-title-main">Levoamphetamine</span> CNS stimulant and isomer of amphetamine

Levoamphetamine is a stimulant medication which is used in the treatment of certain medical conditions. It was previously marketed by itself under the brand name Cydril, but is now available only in combination with dextroamphetamine in varying ratios under brand names like Adderall and Evekeo. The drug is known to increase wakefulness and concentration in association with decreased appetite and fatigue. Pharmaceuticals that contain levoamphetamine are currently indicated and prescribed for the treatment of attention deficit hyperactivity disorder (ADHD), obesity, and narcolepsy in some countries. Levoamphetamine is taken by mouth.

<span class="mw-page-title-main">Monoamine releasing agent</span> Class of compounds

A monoamine releasing agent (MRA), or simply monoamine releaser, is a drug that induces the release of one or more monoamine neurotransmitters from the presynaptic neuron into the synapse, leading to an increase in the extracellular concentrations of the neurotransmitters and hence enhanced signaling by those neurotransmitters. The monoamine neurotransmitters include serotonin, norepinephrine, and dopamine; monoamine releasing agents can induce the release of one or more of these neurotransmitters.

<span class="mw-page-title-main">EPPTB</span> Chemical compound

EPPTB is a drug developed by Hoffmann-La Roche which acts as a potent and selective inverse agonist of the trace amine-associated receptor 1 (TAAR1), with no significant activity at other targets. EPPTB is one of the first selective antagonists developed for the TAAR1, and has been used to demonstrate an important role for TAAR1 in regulation of dopaminergic signaling in the limbic system.

<span class="mw-page-title-main">Monoaminergic activity enhancer</span> Class of compounds in the nervous system

Monoaminergic activity enhancers (MAE), also known as catecholaminergic/serotonergic activity enhancers (CAE/SAE), are a class of drugs that enhance the action potential-evoked release of monoamine neurotransmitters in the nervous system. MAEs are distinct from monoamine releasing agents (MRAs) like amphetamine and fenfluramine in that they do not induce the release of monoamines from synaptic vesicles but rather potentiate only nerve impulse propagation-mediated monoamine release. That is, MAEs increase the amounts of monoamine neurotransmitters released by neurons per electrical impulse.

<span class="mw-page-title-main">Desmethylselegiline</span> Chemical compound

Desmethylselegiline (DMS), also known as norselegiline or as N-propargyl-L-amphetamine, is an active metabolite of selegiline, a medication used in the treatment of Parkinson's disease and depression.

<span class="mw-page-title-main">Pharmacology of selegiline</span> Pharmacology of the antiparkinsonian and antidepressant selegiline

The pharmacology of selegiline pertains to the pharmacodynamic and pharmacokinetic properties of the antiparkinsonian and antidepressant selegiline (L-deprenyl). Selegiline is available in a few different forms, including oral tablets and capsules, orally disintegrating tablets (ODTs), and transdermal patches. These forms have differing pharmacological properties.

<span class="mw-page-title-main">Indolylpropylaminopentane</span> A synthetic monoaminergic activity enhancer drug

Indolylpropylaminopentane (IPAP), also known as α,N-dipropyltryptamine (α,N-DPT), is a monoaminergic activity enhancer (MAE) that is closely related to benzofuranylpropylaminopentane (BPAP) and phenylpropylaminopentane (PPAP). It is a tryptamine derivative and the corresponding analogue of PPAP and BPAP with an indole ring instead of a benzene ring or benzofuran ring, respectively. IPAP is also a positional isomer of N,N-dipropyltryptamine (N,N-DPT).

József Knoll, or Joseph Knoll, was a Hungarian psychopharmacologist known for developing the antiparkinsonian and antidepressant drug selegiline (L-deprenyl).

<span class="mw-page-title-main">Conditioned avoidance response test</span> Test of antipsychotic-like activity

The conditioned avoidance response (CAR) test, also known as the active avoidance test, is an animal test used to identify drugs with antipsychotic-like effects. It is most commonly employed as a two-way active avoidance test with rodents. The test assesses the conditioned ability of an animal to avoid an unpleasant stimulus. Drugs that selectively suppress conditioned avoidance responses without affecting escape behavior are considered to have antipsychotic-like activity. Variations of the test, like testing for enhancement of avoidance and escape responses, have also been used to assess other drug effects, like pro-motivational and antidepressant-like effects.

References

  1. 1 2 3 Gaszner P, Miklya I (January 2006). "Major depression and the synthetic enhancer substances, (-)-deprenyl and R-(-)-1-(benzofuran-2-yl)-2-propylaminopentane". Prog Neuropsychopharmacol Biol Psychiatry. 30 (1): 5–14. doi:10.1016/j.pnpbp.2005.06.004. PMID   16023777. 1-(Benzofuran-2-yl)-2-(3,3,3-trifluoropropyl)-aminopentane HCl [3-F-BPAP], a newly synthetized analogue of (–)-BPAP with low specific activity, significantly antagonized the enhancer effect of (–)-BPAP but left the effect of (–)-deprenyl and (–)-PPAP unchanged. This was the first proof for a difference in the mechanism of action between a PEA-derived enhancer substance and its tryptamine-derived peer (Knoll et al., 2002a).
  2. 1 2 3 4 Shimazu S, Miklya I (May 2004). "Pharmacological studies with endogenous enhancer substances: beta-phenylethylamine, tryptamine, and their synthetic derivatives". Prog Neuropsychopharmacol Biol Psychiatry. 28 (3): 421–427. doi:10.1016/j.pnpbp.2003.11.016. PMID   15093948. A recent study furnished direct evidence for the first time that the mechanism through which selegiline, the PEA-derived synthetic enhancer substance, and (–)- BPAP, the tryptamine-derived synthetic enhancer substance, exert their enhancer effects are not identical. An analogue of (–)-BPAP with a weak enhancer effect antagonized the effect of (–)-BPAP but did not influence the enhancer effect of selegiline (Knoll et al., 2002a). The results suggest the heterogeneity of enhancer receptors. It was proposed in this study that TA receptors function as enhancer receptors (Knoll et al., 2002a). The assumption is supported by the finding of Borowsky et al. (2001) that the TA receptors for PEA and tryptamine are not identical.
  3. 1 2 3 4 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. Convincing indirect proof for specific enhancer receptors in the dopaminergic system was already furnished by a recent study (34). 1-(2-Benzofuryl)-2-(3,3,3-trifluoropropyl) aminopentane HCl (3-F-BPAP) a close structural analogue of BPAP with weak enhancer activity was synthesized with the expectation that the simultaneous administration of this analogue with (–)-BPAP will significantly antagonize the enhancer effect of the latter, proving that they act on the same receptor. The low specific activity of 3-F-BPAP was demonstrated in the rat in the shuttle box. [...] The effect of (–)-BPAP was measured in eight different doses from 0.05 to 10 mg/kg. Even the lowest dose significantly antagonized tetrabenazine-induced inhibition of learning. In contrast, 3-F-BPAP was ineffective in five different doses, ranging from 0.25 to 5.0 mg/kg (34, Table 3). [...] The concurrent administration of 1 mg/kg 3-FBPAP with 0.1 mg/kg (–)-BPAP significantly inhibited the enhancer effect of (–)-BPAP but 1 mg/kg 3-FBPAP did not influence the enhancer effect of 1 mg/kg (–)-BPAP (34, Fig. 2). This is clear indication that the compounds bind to the same receptor to which (–)-BPAP has a much higher affinity than 3-F-BPAP. [...] We studied the effect of 1 and 5 mg/kg (–)-deprenyl in different combinations with 1 and 5 mg/kg 3-F-BPAP and found that 3-F-BPAP left the enhancer effect of (–)-deprenyl unchanged (34, Fig. 2). Furthermore, 3-F-BPAP did not influence the enhancer effect of (–)-PPAP, a (–)- deprenyl analogue free of MAO-B inhibitory potency (34, Fig. 4).
  4. 1 2 3 4 Knoll J (2005). "Enhancer Regulation: A Neurochemical Approach to the Innate and Acquired Drives". The Brain and Its Self: A Neurochemical Concept of the Innate and Acquired Drives. Berlin/Heidelberg: Springer-Verlag. pp. 25–94. doi:10.1007/3-540-27434-0_4. ISBN   978-3-540-23969-7. 1-(2-Benzofuryl)-2-(3,3,3-trifluoropropyl)-aminopentane HCl (3-F-BPAP), a close structural analogue of BPAP with weak enhancer activity, was synthesized with the expectation that the simultaneous administration of this analogue with (−)-BPAP would significantly antagonize the enhancer effect of the latter, proving that they act on the same receptor. The low specific activity of 3-F-BPAP was demonstrated in the rat in the shuttle box. [...] The effect of (−)-BPAP was measured in eight different doses from 0.05 to 10 mg/kg. Even the lowest dose significantly antagonized tetrabenazine-induced inhibition of learning (see Table 3.1). In contrast, 3-F-BPAP was ineffective in five different doses, ranging from 0.25 to 5.0 mg/kg (Table 3 in Knoll et al. 2002a). [...] The concurrent administration of 1 mg/kg 3-F-BPAP with 0.1 mg/kg (−)- BPAP significantly inhibited the enhancer effect of (−)-BPAP, but 1 mg/kg 3-F-BPAP did not influence the enhancer effect of 1 mg/kg (−)-BPAP (Fig. 2 in Knoll et al. 2002a). This is a clear indication that the compounds bind to the same receptor, to which (−)-BPAP has a much higher affinity than 3-F-BPAP. [...] We studied the effect of 1 and 5 mg/kg (−)-deprenyl in different combinations with 1 and 5 mg/kg 3-F-BPAP and found that 3-F-BPAP left the enhancer effect of (−)-deprenyl unchanged (Fig. 3 in Knoll 2002a). Furthermore, 3-F-BPAP did not influence the enhancer effect of (−)-PPAP, the (−)-deprenyl analogue free of MAO-B inhibitory potency (Fig. 4 in Knoll 2002a).
  5. 1 2 3 4 5 Knoll J, Miklya I, Knoll B, Yasusa T, Shimazu S, Yoneda F (September 2002). "1-(Benzofuran-2-yl)-2-(3,3,3-trifluoropropyl)aminopentane HCl, 3-F-BPAP, antagonizes the enhancer effect of (-)-BPAP in the shuttle box and leaves the effect of (-)-deprenyl unchanged". Life Sci. 71 (17): 1975–1984. doi:10.1016/s0024-3205(02)01968-9. PMID   12175892.
  6. ↑ Miklya I (November 2016). "The significance of selegiline/(-)-deprenyl after 50 years in research and therapy (1965-2015)". Mol Psychiatry. 21 (11): 1499–1503. doi:10.1038/mp.2016.127. PMID   27480491. Even the first developed synthetic enhancers, DEP and BPAP, are not identical in their molecular mechanism.52,53
  7. 1 2 Harsing LG, Knoll J, Miklya I (August 2022). "Enhancer Regulation of Dopaminergic Neurochemical Transmission in the Striatum". Int J Mol Sci. 23 (15): 8543. doi: 10.3390/ijms23158543 . PMC   9369307 . PMID   35955676.
  8. 1 2 Harsing LG, Timar J, Miklya I (August 2023). "Striking Neurochemical and Behavioral Differences in the Mode of Action of Selegiline and Rasagiline". Int J Mol Sci. 24 (17): 13334. doi: 10.3390/ijms241713334 . PMC   10487936 . PMID   37686140.


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