Search results for "PAM"

Positron emission tomography in CNS drug discovery and drug monitoring.

2014

Molecular imaging methods such as positron emission tomography (PET) are increasingly involved in the development of new drugs. Using radioactive tracers as imaging probes, PET allows the determination of the pharmacokinetic and pharmacodynamic properties of a drug candidate, via recording target engagement, the pattern of distribution, and metabolism. Because of the noninvasive nature and quantitative end point obtainable by molecular imaging, it seems inherently suited for the examination of a pharmaceutical’s behavior in the brain. Molecular imaging, most especially PET, can therefore be a valuable tool in CNS drug research. In this Perspective, we present the basic principles of PET, th…

A high-quality homology model for the human dopamine transporter validated for drug design purposes.

2018

The human dopamine transporter (hDAT) plays many vital functions within the central nervous system and is thus targeted by many pharmaceutical agents. Dopamine-related therapies are in current development for individuals with dopamine-related disorders including depression, Parkinson's disease, and psychostimulant addictions such as cocaine abuse. Yet, most efforts to develop new dopamine therapies are within costly structure-activity relationship studies. Through structure-based drug design techniques, the binding site of hDAT can be utilized to develop novel selective and potent dopamine therapies at reduced costs. However, no structural models of hDAT specifically validated for rational …

Preclinical evidence of new opioid modulators for the treatment of addiction.

2010

Addiction to opiates is one of the most severe forms of substance dependence, and despite a variety of pharmacological approaches to treat it, relapse is observed in a high percentage of subjects. New pharmacological compounds are necessary to improve the outcome of treatments and reduce adverse side effects. Moreover, drugs that act on the opioid system can also be of benefit in the treatment of alcohol or cocaine addiction. AREA COVERED BY THIS REVIEW: Recent preclinical studies of pharmacological agents for the treatment of opiate addiction (2008 to the present date).The reader will be informed of the latest drugs shown in animal models to modify dependence on opiates and the reinforcing…

Cross-reinstatement between 3,4-methylenedioxypyrovalerone (MDPV) and cocaine using conditioned place preference.

2019

Abstract 3,4-Methylenedioxypyrovalerone (MDPV) is a new psychoactive substance (NPS) considered to be a cocaine-like psychostimulant. The substitution of an established illicit drug as cocaine with an NPS is a pattern of use reported among drug users. The aim of this study was to investigate the relationship between cocaine and MDPV in the reinstatement of the conditioned place preference (CPP) paradigm, in order to establish whether there is cross-reinstatement between the two psychostimulants. Four experimental groups of male OF1 mice were subjected to the CPP paradigm: MDPV-MDPV, Cocaine-Cocaine, Cocaine-MDPV, and MDPV-Cocaine. The first drug refers to the substance with which the animal…

Retraction notice to “Relationship between dopamine D2 receptor occupancy, clinical response, and drug and monoamine metabolites levels in plasma and…

2012

Functionalized Poly(N-isopropylacrylamide)-Based Microgels in Tumor Targeting and Drug Delivery

2021

Over the past several decades, the development of engineered small particles as targeted and drug delivery systems (TDDS) has received great attention thanks to the possibility to overcome the limitations of classical cancer chemotherapy, including targeting incapability, nonspecific action and, consequently, systemic toxicity. Thus, this research aims at using a novel design of Poly(N-isopropylacrylamide) p(NIPAM)-based microgels to specifically target cancer cells and avoid the healthy ones, which is expected to decrease or eliminate the side effects of chemotherapeutic drugs. Smart NIPAM-based microgels were functionalized with acrylic acid and coupled to folic acid (FA), targeting the f…

Verapamil Inhibits the Respiration Rate of Cancer Cells

1986

Calcium antagonists have successfully been used in the treatment of hypertension, cardiac arrhythmias and coronary heart disease. Recent evidence has suggested that such agents may also play a role in the treatment of malignant tumors. Verapamil, a calcium entry blocker, has been reported to enhance the cytotoxicity of several anticancer drugs under in vitro- and in vivo-conditions [1–10]. The effects observed could be explained by an enhanced drug accumulation due to a Verapamil-induced inhibition of the drug efflux from the cancer cells.

Adjuncts for ovarian stimulation: when do we adopt “orphan indications” for approved drugs?

2009

Several drugs, shown to be safe for other uses, have proven to be highly effective adjuncts for ovarian stimulation. The authors evaluate these "orphan" indications and make recommendations so that more patients will benefit from their use.

Pre-Clinical Studies with D-Penicillamine as a Novel Pharmacological Strategy to Treat Alcoholism: Updated Evidences

2017

Ethanol, as other drugs of abuse, is able to activate the ventral tegmental area dopamine (VTA-DA) neurons leading to positively motivational alcohol-seeking behavior and use, and, ultimately to ethanol addiction. In the last decades, the involvement of brain-derived acetaldehyde (ACD) in the ethanol actions in the mesolimbic pathway has been widely demonstrated. Consistent published results have provided a mechanistic support to the use of ACD inactivating agents to block the motivational and reinforcing properties of ethanol. Hence, in the last years, several pre-clinical studies have been performed in order to analyze the effects of the sequestering ACD agents in the prevention of ethano…

Interactions and Monitoring of Antipsychotic Drugs

2012

As a consequence of individualized antipsychotic pharmacotherapy, many patients need more than a single drug, since they do not respond sufficiently to monotherapy. Other patients suffer from comorbid diseases and therefore require additional drugs from other pharmacological classes. Drug combinations, however, can give rise to pharmacokinetic and/or pharmacodynamic drug–drug interactions. Evaluation of pharmacokinetic interactions with antipsychotic drugs must consider substrate, inhibitor, and inducer properties for the cytochrome P450 (CYP) isoenzymes of all combined drugs. For consideration of pharmacodynamic interactions, special attention must be given to effects on dopamine D2, hista…