Review

Authors: C Hiemke, N Bergemann, H W Clement...

Therapeutic drug monitoring (TDM) is the quantification and interpretation of drug concentrations in blood to optimize pharmacotherapy. It considers the interindividual variability of pharmacokinetics and thus enables personalized pharmacotherapy. In psychiatry and neurology, patient populations that may particularly benefit from TDM are children and adolescents, pregnant women, elderly patients, individuals with intellectual disabilities, patients with substance abuse disorders, forensic psychiatric patients or patients with known or suspected pharmacokinetic abnormalities. Non-response at therapeutic doses, uncertain drug adherence, suboptimal tolerability, or pharmacokinetic drug-drug interactions are typical indications for TDM. However, the potential benefits of TDM to optimize pharmacotherapy can only be obtained if the method is adequately integrated in the clinical treatment process. To supply treating physicians and laboratories with valid information on TDM, the TDM task force of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) issued their first guidelines for TDM in psychiatry in 2004. After an update in 2011, it was time for the next update. Following the new guidelines holds the potential to improve neuropsychopharmacotherapy, accelerate the recovery of many patients, and reduce health care costs.

Topics: Drug Monitoring; Guidelines as Topic; Humans; Mental Disorders; Neuropharmacology; Psychopharmacology; Psychotropic Drugs

PubMed: 28910830
DOI: 10.1055/s-0043-116492

Review

Authors: Tahir Hakami

BACKGROUND

Antiseizure drugs (ASDs) are the primary therapy for epilepsy, with more than 20 drugs introduced into clinical practice to date. These drugs are typically grouped by their mechanisms of action and therapeutic spectrum. This article aims to educate non-neurologists and medical students about the new frontiers in the pharmacology of ASDs and presents the current state of the literature on the efficacy and tolerability of these agents.

METHODS

Randomized controlled trials, observational studies, and evidence-based meta-analyses of ASD efficacy and tolerability as initial monotherapy for epileptic seizures and syndromes were identified in PubMed, EMBASE, the Cochrane Library, and Elsevier Clinical Pharmacology.

RESULTS

The choice of ASD varies primarily according to the seizure type. Practical guidelines for ASD selection in patients with new-onset and drug-resistant epilepsy were recently published. The guidelines have shown that the newer-generation drugs, which have unique mechanistic and pharmacokinetic properties, are better tolerated but have similar efficacy compared with the older drugs. Several ASDs are effective as first-line monotherapy in focal seizures, including lamotrigine, carbamazepine, phenytoin, levetiracetam, and zonisamide. Valproate remains the first-line drug for many patients with generalized and unclassified epilepsies. However, valproate should be avoided, if possible, in women of childbearing potential because of teratogenicity. Toxicity profile precludes several drugs from use as first-line treatment, for example, vigabatrin, felbamate, and rufinamide.

CONCLUSIONS

Antiseizure drugs have different pharmacologic profiles that should be considered when selecting and prescribing these agents for epilepsy. These include pharmacokinetic properties, propensity for drug-drug interactions, and adverse effects.

Topics: Anticonvulsants; Epilepsies, Partial; Epilepsy; Epilepsy, Generalized; Humans; Neuropharmacology; Pharmaceutical Preparations; Seizures; Valproic Acid

PubMed: 34296824
DOI: 10.1002/npr2.12196

Review

Authors: Theresa M Carbonaro, Michael B Gatch

N,N-dimethyltryptamine (DMT) is an indole alkaloid widely found in plants and animals. It is best known for producing brief and intense psychedelic effects when ingested. Increasing evidence suggests that endogenous DMT plays important roles for a number of processes in the periphery and central nervous system, and may act as a neurotransmitter. This paper reviews the current literature of both the recreational use of DMT and its potential roles as an endogenous neurotransmitter. Pharmacokinetics, mechanisms of action in the periphery and central nervous system, clinical uses and adverse effects are also reviewed. DMT appears to have limited neurotoxicity and other adverse effects except for intense cardiovascular effects when administered intravenously in large doses. Because of its role in nervous system signaling, DMT may be a useful experimental tool in exploring how the brain works, and may also be a useful clinical tool for treatment of anxiety and psychosis.

Topics: Animals; Brain; Hallucinogens; Humans; Mood Disorders; N,N-Dimethyltryptamine; Neuropharmacology

PubMed: 27126737
DOI: 10.1016/j.brainresbull.2016.04.016

Review

Authors: Ruthie E Wittenberg, Shannon L Wolfman, Mariella De Biasi...

Nicotine is a highly addictive drug found in tobacco that drives its continued use despite the harmful consequences. The initiation of nicotine abuse involves the mesolimbic dopamine system, which contributes to the rewarding sensory stimuli and associative learning processes in the beginning stages of addiction. Nicotine binds to neuronal nicotinic acetylcholine receptors (nAChRs), which come in a diverse collection of subtypes. The nAChRs that contain the α4 and β2 subunits, often in combination with the α6 subunit, are particularly important for nicotine's ability to increase midbrain dopamine neuron firing rates and phasic burst firing. Chronic nicotine exposure results in numerous neuroadaptations, including the upregulation of particular nAChR subtypes associated with long-term desensitization of the receptors. When nicotine is no longer present, for example during attempts to quit smoking, a withdrawal syndrome develops. The expression of physical withdrawal symptoms depends mainly on the α2, α3, α5, and β4 nicotinic subunits in the epithalamic habenular complex and its target regions. Thus, nicotine affects diverse neural systems and an array of nAChR subtypes to mediate the overall addiction process. This article is part of the special issue on 'Contemporary Advances in Nicotine Neuropharmacology'.

Topics: Animals; Brain; Humans; Nicotine; Nicotinic Agonists; Nicotinic Antagonists; Protein Subunits; Receptors, Nicotinic; Tobacco Use Disorder

PubMed: 32738308
DOI: 10.1016/j.neuropharm.2020.108256

Authors: D J Heal, S L Smith, S J Belouin...

This Special Issue of Neuropharmacology on psychedelics provides a timely and comprehensive update on progress following the previous Neuropharmacology Special Issue "Psychedelics: New Doors, Altered Perceptions". Remarkable advances have been made in basic and clinical research on psychedelics in the five years since 2018. It is partly based on the seminar series focused on psilocybin organized by the National Institutes of Health (NIH), USA from April to June 2021, the "NIH Psilocybin Research Speaker Series". Participants were world leading experts, including scientists, medical practitioners, clinical psychologists and oncologists, and attendees from additional disciplines of patient advocacy, law, government science policy and regulatory policy. To provide a global perspective, their contributions are complemented with reviews by some of the world's most eminent scientists in the field. The US Food and Drug Administration (FDA) has granted two breakthrough therapy designations for psilocybin in treatment resistant depression (TRD) in 2018 and major depressive disorder (MDD) in 2019, as well as for MDMA for the treatment of post-traumatic stress disorder (PTSD) in 2017. Clinical trials are in progress to assess the therapeutic value of psilocybin in MDD and TRD, and in other indications such as cancer-related anxiety and depression, anorexia, PTSD, substance use disorders and various types of chronic pain. The contributors' insights should assist basic and applied science for transition of psychedelics from bench to potential mainstream therapies. The implications are global, because FDA approval of these new medicines will increase international interest and efforts.

Topics: Humans; Hallucinogens; Psilocybin; Depressive Disorder, Major; Substance-Related Disorders; Anxiety

PubMed: 37247807
DOI: 10.1016/j.neuropharm.2023.109610

Authors: David Nutt, David Erritzoe, Robin Carhart-Harris...

After a legally mandated, decades-long global arrest of research on psychedelic drugs, investigation of psychedelics in the context of psychiatric disorders is yielding exciting results. Outcomes of neuroscience and clinical research into 5-Hydroxytryptamine 2A (5-HT2A) receptor agonists, such as psilocybin, show promise for addressing a range of serious disorders, including depression and addiction.

Topics: Hallucinogens; Humans; Mental Disorders; Neuropharmacology; Psilocybin; Psychiatry; Serotonin 5-HT2 Receptor Agonists

PubMed: 32243793
DOI: 10.1016/j.cell.2020.03.020

Review

Authors: R Maldonado, P Calvé, A García-Blanco...

Addiction is a chronic brain disease that has dramatic health and socioeconomic consequences worldwide. Multiple approaches have been used for decades to clarify the neurobiological basis of this disease and to identify novel potential treatments. This review summarizes the main brain networks involved in the vulnerability to addiction and specific innovative technological approaches to investigate these neural circuits. First, the evolution of the definition of addiction across the Diagnostic and Statistical Manual of Mental Disorders (DSM) is revised. We next discuss several innovative experimental techniques that, combined with behavioral approaches, have allowed recent critical advances in understanding the neural circuits involved in addiction, including DREADDs, calcium imaging, and electrophysiology. All these techniques have been used to investigate specific neural circuits involved in vulnerability to addiction and have been extremely useful to clarify the neurobiological basis of each specific component of the addictive process. These novel tools targeting specific brain regions are of great interest to further understand the different aspects of this complex disease. This article is part of the special issue on 'Vulnerabilities to Substance Abuse.'.

Topics: Animals; Behavior, Addictive; Brain; Calcium Signaling; Disease Susceptibility; Electroencephalography; Electrophysiological Phenomena; Humans; Illicit Drugs; Nerve Net; Piperazines

PubMed: 33482225
DOI: 10.1016/j.neuropharm.2021.108466

Review

Authors: Sara Marsango, Richard J Ward, Elisa Alvarez-Curto...

G protein-coupled receptors (GPCRs) have been classically described as monomeric entities that function by binding in a 1:1 stoichiometric ratio to both ligand and downstream signalling proteins. However, in recent years, a growing number of studies has supported the hypothesis that these receptors can interact to form dimers and higher order oligomers although the molecular basis for these interactions, the overall quaternary arrangements and the functional importance of GPCR oligomerization remain topics of intense speculation. Muscarinic acetylcholine receptors belong to class A of the GPCR family. Each muscarinic receptor subtype has its own particular distribution throughout the central and peripheral nervous systems. In the central nervous system, muscarinic receptors regulate several sensory, cognitive, and motor functions while, in the peripheral nervous system, they are involved in the regulation of heart rate, stimulation of glandular secretion and smooth muscle contraction. Muscarinic acetylcholine receptors have long been used as a model for the study of GPCR structure and function and to address aspects of GPCR dimerization using a broad range of approaches. In this review, the prevailing knowledge regarding the quaternary arrangement for the various muscarinic acetylcholine receptors has been summarized by discussing work ranging from initial results obtained using more traditional biochemical approaches to those generated with more modern biophysical techniques. This article is part of the Special Issue entitled 'Neuropharmacology on Muscarinic Receptors'.

Topics: Animals; Dimerization; Humans; Receptors, Muscarinic

PubMed: 29146505
DOI: 10.1016/j.neuropharm.2017.11.023

Review

Authors: Joshua A Burk, Sarah A Blumenthal, Eden B Maness...

Early philosophers and psychologists defined and began to describe attention. Beginning in the 1950's, numerous models of attention were developed. This corresponded with an increased understanding of pharmacological approaches to manipulate neurotransmitter systems. The present review focuses on the knowledge that has been gained about these neurotransmitter systems with respect to attentional processing, with emphasis on the functions mediated within the medial prefrontal cortex. Additionally, the use of pharmacotherapies to treat psychiatric conditions characterized by attentional dysfunction are discussed. Future directions include developing a more comprehensive understanding of the neural mechanisms underlying attentional processing and novel pharmacotherapeutic targets for conditions characterized by aberrant attentional processing.

Topics: Animals; Attention; Humans; Neuropharmacology

PubMed: 30092180
DOI: 10.1016/j.ejphar.2018.08.008

Authors: Rona R Ramsay, Philippe De Deurwaerdère, Giuseppe Di Giovanni...

This article is part of a themed section on Updating Neuropathology and Neuropharmacology of Monoaminergic Systems. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.13/issuetoc.

Topics: Animals; Biogenic Monoamines; Depression; Diabetes Mellitus, Type 2; Humans; Mental Disorders; Neuropharmacology

PubMed: 27302283
DOI: 10.1111/bph.13508