2-Phenyl-2-(1-hydroxycycloalkyl)ethylamine derivatives: synthesis and antidepressant activity.

doi:10.1021/JM00172A035

Paper

2-Phenyl-2-(1-hydroxycycloalkyl)ethylamine derivatives: synthesis and antidepressant activity.

Published Oct 1, 1990 · J. Yardley, G. E. Husbands, G. Stack

Journal of medicinal chemistry

Q1 SJR score

126

Citations

2

Influential Citations

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Abstract

A series of 2-phenyl-2-(1-hydroxycycloalkyl)ethylamine derivatives was examined for the ability to inhibit both rat brain imipramine receptor binding and the synaptosomal uptake of norepinephrine (NE) and serotonin (5-HT). Neurotransmitter uptake inhibition was highest for a subset of 2-phenyl-2-(1-hydroxycyclohexyl)dimethylethylamines in which the aryl ring has a halogen or methoxy substituent at the 3- and/or 4-positions. Potential antidepressant activity in this subset was assayed in three rodent models--the antagonism of reserpine-induced hypothermia, the antagonism of histamine-induced ACTH release, and the ability to reduce noradrenergic responsiveness in the rat pineal gland. An acute effect seen in the rat pineal gland with several analogues, including 1-[1-(3,4-dichlorophenyl)-2-(dimethylamino)ethyl]cyclohexanol (23) and 1-[2-(dimethylamino)-1)-(4-methoxyphenyl)ethyl]cyclohexanol (4), was taken as a possible correlate of a rapid onset of antidepressant activity. Compound 4 (venlafaxine) is presently undergoing clinical evaluation.

Non-RCT

Animal Study

Highly Cited

Study Snapshot

2-phenyl-2-(1-hydroxycycloalkyl)ethylamine derivatives show potential antidepressant activity, with venlafaxine showing the highest neurotransmitter uptake inhibition and a rapid onset in rat pineal gland.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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2-Phenyl-2-(1-hydroxycycloalkyl)ethylamine derivatives: synthesis and antidepressant activity.

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References

Citations

Development and Validation of a RP-HPLC Method for the determination of Venlafaxine hydrochloride in bulk and Pharmaceutical Dosage Forms

A simple, accurate, and rapid reverse phase HPLC method was developed and validated for analyzing venlafaxine hydrochloride in bulk and pharmaceutical dosage forms, with a limit of detection of 185ng/ml and quantification limit of 563ng/ml.

Multitargeting nature of muscarinic orthosteric agonists and antagonists

Muscarinic receptors exhibit limited selectivity, but multitargeting drugs may be beneficial for treating diseases like schizophrenia.

Tandem Mass Spectrometry (MS/MS) in the Preclinical Pharmacokinetic Study of a Highly Prescribed SNRI Drug for Depression and Its Application to Oral Extended Release Solid Dosage Formulations in Rabbits

The LC-MS/MS method effectively quantitates venlafaxine and its metabolite O-desmethylvenlafaxine in rabbit plasma, providing valuable information for formulation development and drug safety assessment.

Venlafaxine Caffeic Acid Salt: Synthesis, Structural Characterization, and Hypoglycemic Effect Analysis

The novel venlafaxine-caffeic acid salt shows 16-fold higher solubility and potent hypoglycemic activity, making it a promising candidate for treating major depressive disorder in patients with type 2 diabetes.

Enantioselective Synthesis of α‐Aryl‐β2‐Amino‐Esters by Cooperative Isothiourea and Brønsted Acid Catalysis

This study demonstrates a high-yield, enantioselective synthesis of aryl-2-amino esters using cooperative isothiourea and Brnsted acid catalysis, with potential applications in the synthesis of (S)-Venlafaxine-

Salt or/and cocrystal? The case of the antidepressant drug venlafaxine

The crystallization of venlafaxine in 3,5-dinitrobenzoic acid leads to the formation of a salt and a salt cocrystal, both with superior phase stability and improved solubility compared to the free base.

The Resurrection of Phenotypic Drug Discovery.

Phenotypic drug discovery approaches are resurrected due to increased clinical trial failures due to poor correlation between novel mechanistic targets and the actual disease state.