2-Substituted Cyclopropylamines. I. Derivatives and Analogs of 2-Phenylcyclopropylamine

Kaiser, Carl; Lester, Bruce M.; Zirkle, Charles L.; Burger, Alfred; Davis, Charles S.; Delia, Thomas J.; Zirngibl, Ludwig

doi:10.1021/jm01241a017

Cited by 44 publications

(12 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Optical activity was determined by sending samples for analysis to Robertson Microlite laboratories. While the purity of the isomers was not specifically tested, the optical activity of the separated isomers were nearly identical to that of Kaiser et al, which was reported for the (−) and (+) isomers to be: −30.5 and +31.0 (Kaiser et al, 1962). …”

Section: Methodssupporting

confidence: 71%

See 1 more Smart Citation

The monoamine oxidase (MAO) inhibitor tranylcypromine enhances nicotine self-administration in rats through a mechanism independent of MAO inhibition

et al. 2011

View full text Add to dashboard Cite

Our current study aims to evaluate the mechanisms of tranylcypromine (TCP)-mediated enhancement of nicotine self-administration. We replicated our previous findings which demonstrate that 1-hr pretreatment with TCP (3mg/kg, i.p.) enhances nicotine self-administration (7.5 μg/kg/inj, i.v.) when compared with vehicle-treated rodents. We tested whether TCP-mediated enhancement of nicotine self-administration was due to MAO inhibition or off-target effects by (i) extending the TCP pretreatment time from 1 to 20 hr, and (ii) evaluating the role of the individual TCP stereoisomers in nicotine self-administration studies. While 20-hr and (−)TCP pretreatment induced significant inhibition of MAO (60–90%), animals found nicotine only weakly reinforcing. Furthermore, while both (+) and (±)TCP treatment induced nearly 100% MAO inhibition, (+)TCP pretreated animals took longer to acquire nicotine self-administration compared to (±)TCP pretreated animals. Stable nicotine self-administration in (+)TCP pretreated animals was influenced by nicotinic receptor activation but not nicotine-paired cues. The opposite was found in (±)TCP pretreated animals. Treatment with (−) or (±)TCP increased dopamine and serotonin overflow, while the (+) and (±)TCP treatment enhanced monoamine overflow subsequent to nicotine. Together, our data suggests TCP-enhancement of nicotine self-administration are mediated through mechanisms independent of MAO inhibition, including nicotine-paired cues and monoamine uptake inhibition.

show abstract

Section: Methodssupporting

confidence: 71%

“…The positive and negative stereoisomers were purified from (±)TCP as a tartrate salt following established methods previously described (Kaiser et al, 1962). In short, we combined equal amounts of D-tartaric acid (0.1 moles) with the racemic form of TCP in ethanol.…”

Section: Methodsmentioning

confidence: 99%

The monoamine oxidase (MAO) inhibitor tranylcypromine enhances nicotine self-administration in rats through a mechanism independent of MAO inhibition

et al. 2011

View full text Add to dashboard Cite

show abstract

“…2‐PCPA ( 1 ) was first synthesized by Burger and Yost in 1948 and later, a series of 2‐PCPA derivatives and their MAO‐inhibitory properties were reported . Among all these compounds, 1 was developed as a clinical antidepressant, which is nonselective toward multiple forms of MAO .…”

Section: Introductionmentioning

confidence: 99%

An Overview of Phenylcyclopropylamine Derivatives: Biochemical and Biological Significance and Recent Developments

Khan

Suzuki

Miyata

2012

Medicinal Research Reviews

View full text Add to dashboard Cite

trans-2-Phencylcyclopropylamine (2-PCPA), a potent, clinically used antidepressant, affects monoamine neurotransmitter levels by inhibiting the main metabolizing enzymes, monoamine oxidases (MAOs). However, the antidepressant action of this compound was not fully explained by its effects on MAOs due to its wide variety of biological effects. 2-PCPA also affects depression-associated pathophysiological pathways, and linked with increased levels of trace amines in brain, upregulation of GABAB receptors (where GABA is gamma amino butyric acid), modulation of phospholipid metabolism, and interference with various cytochrome P450 (CYP) enzymes. Consequently, despite its adverse effects and limited clinical applicability, 2-PCPA has attracted interest as a structural scaffold for the development of mechanism-based inhibitors of various enzymes, including lysine-specific demethylase 1 (LSD1), which is a possible target for cancer chemotherapy. In the recent years, many reports have appeared in the literature based on 2-PCPA scaffold and their potential medicinal implications. This review mainly focuses on the medicinal chemistry aspects including drug design, structure-activity relationships (SAR), biological and biochemical properties, and mechanism of actions of 2-PCPA and its derivatives. Furthermore, we also highlight recent advance in this area and discuss their future applications for beneficial therapeutic effects.

show abstract

“…Tranylcypromine (d, l-trans-2-phenylcyclopropylamine) was synthetized by Burger and Yost in 1948 (11). The stereoisomers of tranylcypromine were synthetized by Kaiser and coworkers at Smith Kline & French Laboratories in Philadelphia in 1962 (21). The absolute configuration of tranylcypromine stereoisomers was reported by Riley and Brier in 1972 (33).…”

Section: Introductionmentioning

confidence: 99%

Tranylcypromine Stereoisomers, Monoaminergic Neurotransmission and Behavior. A minireview

Df¹

1980

Pharmacopsychiatry

View full text Add to dashboard Cite

Studies on the effects of the d- and l-stereoisomers of tranylcypromine on locomotor activity, aggressive behavior, hindlimb reflexes, head twitches and behaviors produced by reserpine in rats are reviewed. The d-isomer is found to produce stereotypic behavior and head twitches, to enhance extensor hindlimb reflexes, and to alter effects of reserpine on locomotor activity. The l-isomer is shown to enhance vertical and horizontal locomotor activity and to cause aggressive behavior, but failed to influence hindlimb reflexes, effects of reserpine, or to produce head twitches. Biochemical and pharmacological studies suggest that the d-isomer influences mainly tryptaminergic neurotransmission while the l-isomer affects primarily catecholaminergic neurotransmission. It is concluded that tranylcypromine stereoisomers have stereoselective effects on behavior and monoaminergic neurotransmission. The implications of the findings for the notion that the antidepressant effects of tranylcypromine are due to inhibition of MAO are briefly discussed.

show abstract

2-Substituted Cyclopropylamines. I. Derivatives and Analogs of 2-Phenylcyclopropylamine

Abstract: Fungistatic and bacteriostatic assays were performed by a serial dilution method which has been described previously.1

Cited by 44 publications

References 15 publications

The monoamine oxidase (MAO) inhibitor tranylcypromine enhances nicotine self-administration in rats through a mechanism independent of MAO inhibition

The monoamine oxidase (MAO) inhibitor tranylcypromine enhances nicotine self-administration in rats through a mechanism independent of MAO inhibition

An Overview of Phenylcyclopropylamine Derivatives: Biochemical and Biological Significance and Recent Developments

Tranylcypromine Stereoisomers, Monoaminergic Neurotransmission and Behavior. A minireview

Contact Info

Product

Resources

About