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BACKGROUND Subtypes of sigma (σ) receptors, σ₁ and σ₂, can be pharmacologically distinguished, and each may be involved in substance-abuse disorders. σ-Receptor antagonists block cocaine place conditioning and σ-receptor agonists are self-administered in rats that previously self-administered cocaine. Self-administration of abused drugs has been related to(More)
Methamphetamine interacts with sigma receptors at physiologically relevant concentrations suggesting a potential site for pharmacologic intervention. In the present study, a previous sigma receptor ligand, CM156, was optimized for metabolic stability, and the lead analog was evaluated against the behavioral effects of methamphetamine. Radioligand binding(More)
Cocaine is a highly abused drug without effective pharmacotherapies to treat it. It interacts with sigma (sigma) receptors, providing logical targets for the development of medications to counteract its actions. Cocaine causes toxic and stimulant effects that can be categorized as acute effects such as convulsions and locomotor hyperactivity and subchronic(More)
Cocaine's toxicity can be mitigated by blocking its interaction with sigma-1 receptors. The involvement of sigma-2 receptors remains unclear. To investigate their potential role, we have designed compounds through a convergent synthesis utilizing a highly selective sigma-1 ligand and elements of a selective sigma-2 ligand. Among the synthesized compounds(More)
σ-1 receptor (S1R) radioligands have the potential to detect and monitor various neurological diseases. Herein we report the synthesis, radiofluorination, and evaluation of a new S1R ligand 6-(3-fluoropropyl)-3-(2-(azepan-1-yl)ethyl)benzo[d]thiazol-2(3H)-one ([(18)F]FTC-146, [(18)F]13). [(18)F]13 was synthesized by nucleophilic fluorination, affording a(More)
Sigma receptors have been well documented as a protein target for cocaine and have been shown to be involved in the toxic and stimulant actions of cocaine. Strategies to reduce the access of cocaine to sigma receptors have included antisense oligonucleotides to the sigma-1 receptor protein as well as small molecule ligand with affinity for sigma receptor(More)
UNLABELLED The noninvasive imaging of σ-1 receptors (S1Rs) could provide insight into their role in different diseases and lead to novel diagnostic/treatment strategies. The main objective of this study was to assess the S1R radiotracer (18)F-FTC-146 in rats. Preliminary squirrel monkey imaging and human serum/liver microsome studies were performed to gain(More)
A series of N-(2-(5-fluoro-2-(4-fluorophenylthio)benzo[b]thiophen-3-yl)ethyl)acylamides was synthesized and evaluated for binding affinity and intrinsic activity at melatonin receptors. The affinity of each compound for the melatonin receptors was determined by binding studies on cloned human MT1 and MT2 receptors expressed in CHO cells. Agonist and(More)
The sigma-2 receptor (S2R) is a potential therapeutic target for cancer and neuronal diseases. However, the identity of the S2R has remained a matter of debate. Historically, the S2R has been defined as (1) a binding site with high affinity to 1,3-di-o-tolylguanidine (DTG) and haloperidol but not to the selective sigma-1 receptor ligand (+)-pentazocine, and(More)
Methamphetamine (METH) is a highly addictive psychostimulant drug of abuse. Low and high dose administration of METH leads to locomotor stimulation, and dopaminergic and serotonergic neurotoxicity, respectively. The behavioral stimulant and neurotoxic effects of METH can contribute to addiction and other neuropsychiatric disorders, thus necessitating the(More)