Selegiline, an irreversible monoamine oxidase-B (MAO-B) inhibitor, is under investigation as a treatment for cocaine relapse prevention. To evaluate its safety, human volunteers (n = 5) received intravenous cocaine (0, 20 and 40 mg, 1 h apart) following treatment with placebo or selegiline (10 mg, p.o.). Cocaine increased heart rate, blood pressure, pupil diameter and subjective indices of euphoria and craving. Selegiline produced no measureable effects, except for miosis, and did not alter the effects of cocaine. These data suggest that selegiline may be safely administered in combination with cocaine, and that selegiline is unlikely to increase reinforcing effects of cocaine.
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http://dx.doi.org/10.1016/0376-8716(95)01137-n | DOI Listing |
Med Chem
January 2025
Department of Neurosurgery, The 940th Hospital of Joint Logistics Support force of Chinese People's Liberation Army, Lanzhou, China.
Background: Neurodegenerative diseases are a group of disorders characterized by progressive neuronal degeneration and death, of which Alzheimer's disease and Parkinson's disease are the most common. These diseases are closely associated with increased expression of monoamine oxidase B (MAO-B), an important enzyme that regulates neurotransmitter concentration, and its overactivity leads to oxidative stress and neurotoxicity, accelerating the progression of neurodegenerative diseases. Therefore, the development of effective MAO-B inhibitors is important for the treatment of neurodegenerative diseases.
View Article and Find Full Text PDFMol Divers
January 2025
State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian, 116024, Liaoning, China.
Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases. Given the multifactorial pathophysiology of AD, monotargeted agents can only alleviate symptoms but not cure AD. Acetylcholinesterase (AChE) and Monoamine oxidase B (MAO-B) are two key targets in the treatment of AD, molecules that inhibiting both targets are considered promising avenue to develop more effective AD therapies.
View Article and Find Full Text PDFJ Med Chem
January 2025
Consejo Superior de Investigaciones Científicas (IQM-CSIC), Instituto de Química Médica, 28006 Madrid, Spain.
Parkinson's disease (PD), the second most common neurodegenerative disorder, affects around 10 million people worldwide. It is a multifactorial disease marked by dopaminergic neuron loss with oxidative stress (OS) and neuroinflammation as key pathological drivers. Current treatments focus on dopamine replacement and are symptomatic, underscoring the urgent need for disease-modifying therapies.
View Article and Find Full Text PDFACS Med Chem Lett
January 2025
Department of Pharmaceutical Chemistry, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra 425405, India.
Linezolid, a widely used oxazolidinone antibiotic, exhibits potent activity against resistant bacterial infections but is associated with serotonergic toxicity, primarily due to its inhibition of monoamine oxidase (MAO). MAOs, consisting of MAO-A and MAO-B isoforms, play crucial roles in neurotransmitter metabolism, with implications for neurodegenerative disorders like Parkinson's and Alzheimer's diseases. This study aims to optimize Linezolid's structure to transform it into a selective MAO-B inhibitor.
View Article and Find Full Text PDFCurr Top Med Chem
January 2025
Department of Neurosurgery, The 940th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army, Lanzhou, 730000 China.
Background: 6-hydroxybenzothiazole-2-carboxamide is a novel, potent, and specific monoamine oxidase B inhibitor that can be used to study the structure of molecules and come up with new ways to protect neurons.
Objective: The objective of this work was to create an effective model using derivatives of 6- hydroxybenzothiazole-2-carboxamide and establish a dependable predictive foundation for the development of neuroprotective monoamine oxidase B inhibitors for the treatment of neurodegenerative diseases.
Methods: The construction and optimization of all compounds were carried out sequentially using ChemDraw software and Sybyl-X software.
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