Psychotropic drug

About: Psychotropic drug is a research topic. Over the lifetime, 2309 publications have been published within this topic receiving 54070 citations.

Status and Prospects for Psychopharmacology

Abstract: Modern psychopharmacology has been evolving since the 1950s. Its contributions have been enormous and of fundamental importance to modern psychiatric therapeutics, encouraging and enabling the shift away from long-term institutional care, to brief inpatient interventions for crises, and reliance on ambulatory care. In addition, the clinical benefits provided by much of psychiatric chemotherapy, though typically incomplete, have stimulated decades of renewed efforts to develop a more biomedically based theoretical and academic psychiatry. In addition, the psychopharmaceutical industry has been especially successful in blending science and business to provide products of considerable social value.

Discovery of the First in Class Drug for Intractable Itch, Nalfurafine Hydrochloride

Abstract: Nalfurafine hydrochloride (1) was launched on March of 2009 in Japan as the first in class non-narcotic opioid drug for intractable itch caused by haemodialysis. Rational medicinal chemistry effort led us to obtain the morphinan derivative, which is a new chemical class of opioid κ-agonist without the [N-C-C-N(sp2)] pharmacophore sequence of the typical U-50488H derivatives. The applicability of “Message-Address Concept” and “Accessory Site Hypothesis” in the development of the opioid κ-agonist could also be proven. Nalfurafine hydrochloride (1) showed significant opioid κ-agonist activity and induced neither aversion nor preference in rats on the CPP (Conditioned Place Preference) test. No dependence sign was observed in monkey on the self-administration test. This compound was approved without legal narcotic nor psychotropic drug control after a clinical evaluation on human. Details on design rationale and medicinal chemistry of this novel drug will be discussed.

Drugs and confusional states

Abstract: A confusional state is a happening which may be transient or may become permanent, in which an individual is forgetful and disorientated in time, space and person. It may be associated with behavioural disturbance varying from apathy or obtundity to delirium or mania. Such states are encountered frequently in elderly patients due to a broad spectrum of clinical causes. They are episodes of acute malfunction of the brain. The effect of drugs in either causing or treating them will, therefore, hinge on their action on this target organ.

Searching for the molecular basis of bipolar disorder.

Abstract: Maniaanddepressionwerefirstdescribedover twomillennia ago, making bipolar disorder one of the oldest mental disorders. Lithium is the oldest psychotropic drug and is still positionedasoneof thefirst-choicedrugs forbipolardisorder (1). Although other mood stabilizers and antipsychotics are also used for the treatment of bipolar disorder, most of them were originally developed for other diseases such as epilepsy and schizophrenia. Specific efficacy of lithium ions, aswell as high heritability of bipolar disorder, suggests that molecular dysfunction plays a role in this disorder. To comprehensively search for the molecular basis of bipolar disorder, genetics and gene expression analyses of postmortembrains should be major strategies. At the endof the lastmillennium, the development ofDNA microarray and completion of the human genome project enabled comprehensive analysis of all gene transcripts in the brain.Researchersexpected that themolecular basis ofbipolar disorderwouldbeclearly elucidatedusing this technology, and a number of studies mainly focusing on the prefrontal cortex were conducted. However, the initial enthusiasm was discouraged by the lack of reproducibility among multiple studies (2).Thedifficulty in replicatinggeneexpressionfindings mayhave arisen frommultiple factors, including technological limitations, small sample numbers, medication effects, and postmortemandantemortemchanges.Our lackof knowledge about the brain region responsible for bipolar disorder is also an issue that should be considered. Development of next-generation sequencing technologies enabledmore comprehensive analysis ofDNA sequences and gene expression.Whole-genomeor exomeanalysis of bipolar disorder using next-generation sequencing (3), as well as transcriptome analysis by next-generation sequencing, now referred to as RNA sequencing (4), has recently been applied to researchonbipolardisorder.UsingRNAsequencing analysis, all transcripts, including various alternative splicing isoforms and previously unidentified transcripts, can be analyzed, allowingforadynamicrangelargerthanthatofDNAmicroarray analysis. However, comprehensive analysis of RNA is hampered by the existence of abundant rRNA, which catalyzes protein synthesis, but its sequence is not related to amino acid residue sequences of translated proteins. It is now possible to eliminate rRNA from RNA samples using a recently developed experimental technique. In this issue of the Journal, Cruceanu et al. (5)first applied RNAsequencingwith rRNAdeprivation inorder to search for molecules altered in the brains of patients with bipolar disorder. They analyzed the anterior cingulate cortex, which plays a role in regulating emotion and is the most established candidate brain region of bipolar disorder (6). They identified that 10 candidate genesweredifferentially expressed in the anterior cingulate cortex of 13 patients with bipolar disorder relative to 13 comparison subjects, and all of them were downregulated. These findings were verified in the published data using an independent sample set. Interestingly, the list contained three genes encodingGproteincoupled receptors, including CHRM2 encoding a muscarinictype acetylcholine receptor and SSTR2 encoding a somatostatin receptor. G protein-coupled receptors include neurotransmitter and hormone receptors and are major targets of currently available psychotropic drugs. Using bioinformatics analysis, Cruceanu et al. found that G protein-coupled receptor genes were statistically enriched among all differentially expressed genes associated with bipolardisorder.Theseresults are consistent with a previous report using DNA microarrays (7). To rule out the possibility of medication effects, Cruceanu et al. studied the effect of mood-stabilizing drugs on gene expressioninneuralprogenitorcellsderivedfromhuman-induced pluripotent stem cells. Some of the top 10 genes differentially expressed in bipolar disorder were downregulated by mood stabilizers, suggesting that the original finding might be affected by medication. However, one of the 10 downregulated genes,DIRAS2,wasupregulatedbyall threemoodstabilizers, suggesting that the downregulation of this gene in the postmortem brainmight be related to the pathophysiology of bipolar disorder. Additionally, isoform-level analysis successfully identified that a change in a specific alternatively splicedCHRM isoformresulted in the observed alteration in CHRM. RNA sequencing canmeasure noncodingRNA (ncRNA), in addition to mRNA that encode proteins. It was previously believedthatonly1%22%ofthegenomewasprotein-encoding and functional, but it was ultimately discovered that nearly 70% of the genome is transcribed into RNA (8). The function of ncRNA is not completely understood, and its differential To comprehensively search for the molecular basis of bipolar disorder, genetics and gene expression analyses of postmortem brains should be major strategies.