This has then been bridged to a system of potentially indefinite detention, justified primarily on the police powers of the state but not exclusive of at least an implied rehabilitative intent. The legal definition of personality disorder as applied to sexual offenders is distinct from how personality disorders have more recently been Inhibitors,research,lifescience,medical viewed in the civil commitment process. Some states have excluded personality disorders (Arizona) or specifically ASPD (Florida),

from their definition of mental illness for the purposes of civil commitment.38 Limited available mental health Ipatasertib resources have been focused on acute intervention and treatment of psychoses, major affective disorders, and dementias. Personality-disordered individuals are often excluded from treatment programs and settings. This in turn contrasts with the acceptance of personality disorders as a listed impairment Inhibitors,research,lifescience,medical to warrant disability status under Social Security Disability.39 The Americans with Disabilities Act40 also extends to any mental disorder, but specifically excludes personality Inhibitors,research,lifescience,medical traits that fall short of a formal diagnosis.38 Although

there is some argument to the contrary,41 within the criminal justice system, there has been a strong push to exclude personality disorders, specifically ASPD, from the types Inhibitors,research,lifescience,medical of mental illnesses potentially significant enough to warrant exculpation of fault or consideration of decreased criminal responsibility. The American Law Institute Model Penal Code,42 which

has been adopted in a number of jurisdictions, proposed the exclusion of ASPD by defining mental disease or defect to not include “an abnormality manifested only by repeated criminal or otherwise antisocial conduct.” The federal standard for insanity requires the presence of “a severe mental disease or defect” which is most often interpreted to not include personality disorders as the sole diagnoses of concern.43 Some state statutes (ie, California and Oregon) go as far as excluding Inhibitors,research,lifescience,medical all personality disorders with respect to the insanity defense.44 The Supreme Court in Foucha v. Louisiana45 accepted expert testimony that ASPD was not a mental MycoClean Mycoplasma Removal Kit illness for the purpose of detention of individuals after being found not guilty by reason of insanity. Identification of ASPD generally does not support leniency or treatment recommendations at the time of sentencing, and in capital sentencing proceedings is often presented as an aggravating factor. In contrast, in a New Jersey Supreme Court case, State v. Galloway, the Court held that a defendant’s BPD was capable of impacting cognitive functioning such that the elements of the mental state required for the crime of murder could not be met (eg, purposeful action).

Under this scenario, the alterations of DLPFC circuitry in schizophrenia may render it unable to support higher levels of working memory load, rendering the impaired performance in schizophrenia analogous to the immature levels of working memory function seen

in children.93,94 Neuroplastic responses as targets for treatment The findings reviewed Inhibitors,research,lifescience,medical above indicate that working memory and related cognitive impairments in schizophrenia are likely the result of a complex set of alterations in prefrontal excitatory and inhibitory circuitry. Some of these alterations appear to be Crenolanib deleterious causes or consequences of disturbances in the functional architecture of the DLPFC and Inhibitors,research,lifescience,medical interconnected brain regions, whereas others may be best explained as compensatory responses. In each case, they reflect the morphological and molecular neuroplasticity of DLPFC circuitry in a disease state. Understanding whether the disease-related change in a given molecule is a consequence or compensation in the disease process has Inhibitors,research,lifescience,medical important implications both for the nature of activity of the drugs designed against that target and for the potential therapeutic value of the target. For example, is the neuroplastic capacity of cortical

circuitry sufficiently limited that pharmacological augmentation of a compensatory response is feasible? The results of a recent proofof -concept clinical trial suggest that this may be the case. For example, the idea that GABAA receptors α2 subunits are upregulated in pyramidal neurons due to

Inhibitors,research,lifescience,medical a deficit in GABA input from chandelier neurons led to the use of a novel, positive allosteric modulator of this receptor subtype that improved both working memory Inhibitors,research,lifescience,medical function and prefrontal gamma band oscillations in a small randomized controlled trial of subjects with schizophrenia.95 Given the marked developmental changes that occur in each of these systems during adolescence, this type of pharmacological intervention may have particular value as a treatment strategy for high-risk adolescents in the prodromal phase of the illness. However, the effectiveness and safety of such interventions requires a fuller understanding of the maturation of these neural circuits, of the functional consequences of these circuitry changes and of the vulnerability of these developmental processes old to pharmacological agents. Acknowledgments Cited work conducted by the author was supported by NIH grants MH045156, MH051234 and MH043784. Selected abbreviations and acronyms CCK cholecystokinin DLPFC dorsolateral prefrontal cortex GABA γ-aminobutyric acid GAD glutamic acid decarboxylase GAT GABA membrane transporter NMDA N-methyl-D-aspartic acid PV parvalbumin Notes Disclosure/conflict of interest: David A.

Subjective well-being is at least a valuable addition to objective (?) psychopathology, and should become an integral part of shared decision-making. A better consideration of the patients’ perspective can improve therapeutic alliance, medication adherence, and, finally, the long-term prognosis. Selected abbreviations and acronyms PANSS Positive and Negative Syndrome Scale SOHO Schizophrenia Outpatient Health Outcomes study SUD substance

use disorder SW subjective well-being SWN Subjective Well-being under Neuroleptic treatment
For the past half-century or so, the US Food and Drug Administration (FDA) has licensed drugs for use in schizophrenia only if they Inhibitors,research,lifescience,medical reduced the positive symptoms of psychosis. This limitation was identified as a bottleneck preventing the identification and development of novel R428 supplier treatments for the problems experienced by schizophrenia patients.1,2 Implicitly, the FDA operated from the assumption that one must treat the entire disorder

with one compound, Inhibitors,research,lifescience,medical rather Inhibitors,research,lifescience,medical than treat specific clinical problems with specific compounds. It has become widely accepted that a cluster of cognitive deficits – which have been long recognized as being important aspects of schizophrenia – are not treated adequately, if at all, by existing antipsychotic treatments.2,3 Furthermore, evidence has accumulated that these cognitive Inhibitors,research,lifescience,medical deficits are largely responsible for the disappointingly poor functional outcome demonstrated by antipsychotic-treated patients with schizophrenia.4 Thus, despite the fact that many antipsychotic treatments have been identified and licensed, the cognitive deficits remain as clinical problems in schizophrenia,

and most patients cannot work. The Inhibitors,research,lifescience,medical MATRICS program MATRICS: moving beyond antipsychotics In response to the identification of the bottleneck limiting the development of treatments specifically directed at the cognitive deficits in schizophrenia, the US National Institute of Mental Health (NIMH) developed the Measurement And Treatment Research to Improve Cognition in Schizophrenia (MATRICS) program. Florfenicol MATRICS set out to develop a broad consensus regarding the nature of the cognitive impairments in schizophrenia and how they might best be assessed and treated.5 The MATRICS approach to the problem is to treat cognitive deficits and psychotic symptoms separately. The NIMH awarded the MATRICS contract to the University of California Los Angeles (UCLA) (Drs Stephen Marder and Michael Green, Co-principal Investigators) in 2002. Over the subsequent 2 years, MATRICS gathered the relevant stakeholders in both industry and academia to achieve a consensus and establish a clear path that would enable the FDA to consider registering compounds intended to treat cognitive deficits in schizophrenia, independently of treating psychosis per se.

The sensitivity of different cell types to N-BPs most likely depends largely on their ability to internalize sufficient amounts of N-BPs to inhibit FPP synthase. In view of the pharmacokinetic

concerns that limit the anticancer activity of ZOL, in the last decade the scientists have defined a series of pharmacological and molecular strategies. Some approach was represented by the design of rationale-based drug combinations and the improvement of the pharmacokinetic profile. Inhibitors,research,lifescience,medical Evidence from both in vitro and in vivo models indicated a http://www.selleckchem.com/products/U0126.html synergistic antitumor activity of N-BPs when used in combination with either cytotoxic drugs or targeted molecular therapies [69]. Based on the relevance of the farnesylation inhibitory effects on antitumour activity of N-BPs, the farnesyl transferase inhibitor (FTI) R115777 was used together with PAM or ZOL, and the effects of the combination treatment on growth inhibition and apoptosis were evaluated.

N-BPs and FTI given in combination were strongly synergistic Inhibitors,research,lifescience,medical [70]. Notably, low concentrations of FTI induced a strong Inhibitors,research,lifescience,medical increase of Ras expression with only a moderate reduction of Ras activity that was, on the other hand, significantly reduced by the combined treatment [70]. These data suggested that escape mechanisms for the inhibition of isoprenylation of Ras might be based on the geranylgeranylation or other prenylating processes [74]. The addition of farnesol to cells Inhibitors,research,lifescience,medical treated with the combination abolished the effects of the N-BPs/FTI combination on apoptosis and on the activity of the signaling molecules, suggesting that the synergistic growth-inhibitory and proapoptotic effects produced by the Inhibitors,research,lifescience,medical N-BPs/FTI combination involved the inhibition of both Erk and Akt survival pathways acting in these cells in a Ras-dependent

fashion [70]. A synergistic interaction between R115777 and ZOL was also found on both androgen-independent PC3 and androgen-dependent LNCaP prostate cancer cell lines [70], and the effects were attributed to enhanced apoptosis and inactivation of Erk and Akt. Several papers reported the significant cytostatic and cytotoxic effects of docetaxel (DTX) and ZOL on the hormone- sensitive prostate cancer cell line, LNCaP [17, 75, 76]. In details, the highest inhibition of cell proliferation was observed after DTX exposure and Methisazone was already evident at concentrations 200-fold lower than the plasma peak level. Fabbri et al. hypothesized the use of low DTX doses in concomitance with and followed by a prolonged ZOL exposure to reduce the prostatic tumour cell population and to rapidly induce eradication of hormone-resistant cells present in hormone-responsive tumours, without compromising the use of conventional-dose DTX for the first-line treatment for hormone-sensitive prostate cancer.

73,74 The antibody response is particularly heterogeneous, and many efforts are needed to fully comprehend its clinical significance.75 It is exactly the potent nature of these agents that elicits concerns regarding the side effects they may cause. Similar to other agents

that suppress the immune system, the two main concerns are increased incidence of malignancies and serious infections. There is an inherent difficulty to measure cancer risk for patients treated by anti-TNF agents only because many are treated by combination with immunosuppressives such as thiopurines and steroids. In one study using meta-analysis, the standardized incidence ration of Inhibitors,research,lifescience,medical lymphoma in IBD patients Inhibitors,research,lifescience,medical treated by anti-TNF was estimated to be 1.7 as compared to patients treated by immunomodulation only.76 However, in a cohort of 6273 CD patients

treated by infliximab and followed for 5 years no increased risk for lymphoma was noted. It is noteworthy that steroid treatment, narcotic analgesic treatment, and advanced age were risk factors for increased mortality, and that EGFR assay disease severity, steroid treatment, narcotic Inhibitors,research,lifescience,medical analgesic treatment, and infliximab were risk factors for serious infections.77 The use of these potent medications is further complicated by the fact that response rates are variable. Thus, in a meta-analysis the number needed to treat for induction of remission by thiopurines was five,59 and for maintenance of remission it was six.60 Response rates in individual trials ranged from 67%78 to as low Inhibitors,research,lifescience,medical as 30%.72 The response to anti-TNF agents is also not universal with approximately 20%–30% being primary non-responders79 and 23%–46% or 5%–13% losing response during treatment depending on the definition of LOR.75 The main mechanism for LOR is immunogenicity towards the anti-TNF agent, a phenomenon which can be partially prevented both by concurrent co-treatment Inhibitors,research,lifescience,medical with immunomodulators67 and possibly also after the occurrence of anti-drug antibodies.80 Taken together, the treatment of CD presents a highly complex mosaic of pathophysiologic mechanisms, disease patterns which

are diverse on presentation and change during its course, uncertainty regarding response to drugs, drug interactions which can Thiamine-diphosphate kinase be beneficial but may also potentiate significant and even lethal side effects, and lack of proof regarding their long-term efficacy to change the course of disease. This therapeutic environment creates numerous situations in which decisions have to be taken under conditions of uncertainty, and eventually the final decision depends not only on facts, but also on the personality and subjective points of view of both the patient and physician. It is very hard to form strict treatment guidelines that will fit all CD patients, and tailoring therapy would be the only truly valid solution.

Methadone dose-QTc interval correlation was significant for men (r=0.210, p=0.0014) but not for women (r=0.164, p=0.2363). Over six-months, 60.7% of patients developed an increase in their QTc interval compared with baseline measurements. QTc interval significantly increased in men

(from 418.5 to 426.9 msec, p<0.0001) but not in women (from 437.7 to 441.1 msec, p=0.468). Inhibitors,research,lifescience,medical The authors concluded that (1) low-dose methadone treatment demonstrates dose-dependent QTc interval prolongation and links to significant QTc interval lengthening within six months of starting methadone treatment and (2) men are more susceptible than women are to low-dose methadone-associated QTc interval prolongation. Martell et al. [2005] prospectively assessed methadone (20-200 mg/day) effects on QTc intervals in 160 patients

possessing varying numbers of risk factors for QTc interval prolongation. Women had significantly longer QTc intervals than men at baseline did. At six-month Inhibitors,research,lifescience,medical follow-up, Selleck AT13387 however, factors associated with Inhibitors,research,lifescience,medical greater QTc interval prolongation included male sex and methadone dose at which time 13% of men and 11% of women demonstrated QTc interval prolongation. At 12-month follow-up, methadone dose marginally linked to greater QTc interval prolongation at which time 20% of men and 2% of women showed QTc interval prolongation. No cases of TdP appeared in this study. Their work [Martell et al. 2005] coupled with others [Maremmani et al. 2005; Sticherling et al. 2005] suggest that more than 80% of patients in methadone Inhibitors,research,lifescience,medical maintenance programs have some degree of QTc interval prolongation as discussed earlier. Men are more likely to abuse drugs than women are. Zickler [2000] traces this finding to opportunities to

use drugs of abuse. This Inhibitors,research,lifescience,medical observation applies to heroin abusers and, therefore, subsequent abusers requiring methadone maintenance therapy. Among our adults, 19 of 32 case reports (59.4%) involved men (Tables 1). In the Hanon et al. [2010] series, 9 of 12 (75%) cases were men. In the Chang et al. [2011] series, 229 of 283 (80.9%) subjects were men. If methadone was the main SB-3CT risk factor for TdP and uniformly led to QTc interval prolongation among women and men in the cases under discussion, we would expect this drug to maintain the 2:1 F:M ratio found in non-methadone psychotropic drug-induced cases of QTc interval prolongation and TdP [Vieweg et al. 2009; Vieweg et al. 2011]. We believe the preponderance of male methadone cases is because men are much more likely than women to require methadone treatment for a variety of reasons and this findings overrides greater female vulnerability to drug-induced QTc interval prolongation and TdP [Makkar et al. 1993]. Risk factors for QTc interval prolongation and TdP We have reviewed risk factors for QTc interval prolongation and TdP previously [Vieweg et al. 2009].

Moreover, no data are present in the literature concerning the nanomaterials exposure and other forms of cell death including anoikis, entosis, parthanatos, netosis, and cornification. For example, although numerous studies have been performed on keratinocytes, none of these has rated cornification, a cell death subroutine restricted to keratinocytes and functionally linked to the generation of the stratum corneum of the epidermis [38]. Inhibitors,research,lifescience,medical It will be of considerable interest to establish whether these various cell death modalities are associated with the intent of identifying a structure-activity relationship and delineating the mechanisms

by which these interactions occur. In addition to the established paradigms of nanomaterials toxicity, the study of their interactions with Inhibitors,research,lifescience,medical the death signalling pathways could potentially have many important human pathological outcomes, including cancer, metabolic disorders, and neurodegenerative disorders. Conflict of Interests The authors declare Inhibitors,research,lifescience,medical that they have no conflict of interests. Acknowledgment This work is supported by the Italian Ministry of the University and Scientific Research. Abbreviations Ag+: Silver ions ATG: Autophagy-related

gene Bcl-2: B-cell lymphoma 2 BH3: Bcl-2 homology domain 3 BID: BH3-interacting Inhibitors,research,lifescience,medical domain death agonist Bmf: Bcl-2-modifying factor CNTs: Carbon nanotubes CoCr: Cobalt-chrome DNA: Deoxyribonucleic acid EDTA: Ethylenediaminetetraacetic acid ER: Endoplasmic reticulum FDA: Food and Drug Administration HCS: High-content screening HTS: High-throughput screening IL: Interleukin MOMP: Mitochondrial outer membrane permeabilization Inhibitors,research,lifescience,medical MWCNTs: Multiwall carbon nanotubes NADPH: Nicotinamide adenine dinucleotide phosphate NCCD: Nomenclature Committee on Cell Death PAMAM: Cationic polyamidoamine PANI: Polyaniline PEG-PE: Poly(ethylene

glycol)-phosphoethanolamine RIP: Receptor-interacting protein kinase RNA: Ribonucleic acid RNS: Reactive nitrogen species ROS: Reactive oxygen species SiO2: Florfenicol Silicon dioxide siRNA: Small interfering RNA SWCNTs: Single-walled carbon nanotubes tBID: Truncated BID TiO2: Titanium dioxide ZnO: Zinc oxide.
New drugs for treating eye diseases have been developed over the past decade and are very unique for each eye diseases, such as, glaucoma, cataracts, and age-related macular degeneration (AMD). It is estimated that 1.6 million BMS-754807 order adults in the USA over the age of 50 and above suffer from age-related macular degeneration and about 200,000 cases are diagnosed annually. Worldwide, about 500,000 cases are diagnosed annually [1]. Drugs currently utilized for AMD are delivered via repeated intravitreal injections of the drug into the eye.

Summary of current gene-finding

studies At both the technical/molecular and statistical/Ku-0059436 supplier conceptual levels, the science of gene discovery in complex disease genetics is moving rapidly. By the time this paper is published, new developments are sure to have arisen. As is common in science in the state of rapid flux, the direction ahead is far from clear. How will the modest Inhibitors,research,lifescience,medical but hard-fought advances obtained in more traditional positional cloning and candidate gene work integrate with the new findings from GWAS? How will the commonvariant SNP-based approach inter-relate with the emerging rare-variant copy number variant findings? Will advances in phenotypic assessment or endophenotypes provide critical new insights? How will the burgeoning fields of bioinformatics, expression arrays, and proteomics

impact on our gene-finding efforts? One emerging consensus is that the field needs to move from a “gene-centric” approach toward one that considers “gene networks.” For example, many of the candidate genes discussed above are involved in glutamatergic neurotransmission, Inhibitors,research,lifescience,medical which may be an important systemic element in the etiology of schizophrenia. Although a detailed discussion of this theory is outside the scope of this summary, recent reviews of the genetic183 and neuroscience184 data and evidence from other studies highlight the positions of the gene products of NRG1, COMT, and possibly DTNBP1 among others, Inhibitors,research,lifescience,medical in the Inhibitors,research,lifescience,medical biochemical and functional pathways influencing the glutamatergic system. Many other possible networks may be involved in the etiology of schizophrenia that, if properly articulated, could aid in our gene-discovery efforts. Conclusion We have attempted in this article to review the rapidly evolving field of psychiatric Inhibitors,research,lifescience,medical genetics. In the section on genetic epidemiology,

we took a conceptual approach focusing on a range of the most interesting questions now being confronted by the field, with the goal of giving the reader a “feel” for the issues. While examining a wide range of disorders, we focused on substance use and externalizing disorders because they clearly illustrated the points we wanted to make. In the section on gene-finding, we decided it would be more useful to “drill down” and illustrate our important themes by focusing on one disorder click here – schizophrenia. The major theme that cuts across these two sections is the complexity of the pathways from genetic variation to psychiatric and substance use disorders. Results of the last 20 years have shown that the early prior simple hypothesis of large effect genes that directly causes psychiatric illness was seriously misplaced. We now know that multiple gene variants (as well as – for at least some disorders – genomic rearrangements) are involved at the DNA level. These genetic risk factors then act and interact with each other and with the environment in a complex developmental “dance” to produce individuals at high versus low risk of illness.

Several groups have begun to selleck screening library characterize the early versus late prodromal period.52,71 For example,

a treatment trial underway in Germany has randomized early-phase prodromal participants to receive a program of CBT or clinical management and randomized late-stage prodromal participants to clinical management alone or in conjunction with AP medication.71 Results from such studies will contribute to our understanding of when treatment should be most profitably initiated, what type of treatment Inhibitors,research,lifescience,medical is most appropriate for each prodromal phase, and the criteria most helpful in evaluating short-term treatment effects. This shift in focus may bring about novel interventions such as the use of newly marketed SGAPs, ADs, cognitive enhancers, glycine, /-cycloserine, hormones, and Inhibitors,research,lifescience,medical psychosocial interventions that target specific skill deficits (eg, social skills group). In addition, a collaborative effort under the leadership of Heinssen involving several prodromal research groups in the USA and Canada

(Principal Investigators: Addington, Inhibitors,research,lifescience,medical Cadenhead, Cannon, Cornblatt, McGlashan, Perkins, Seidman, Tsuang, Walker, and Woods), referred to as the North American Prodromal Longitudinal Study (NAPLS), has been recently formed to provide a common database with a large prodromal sample. This collaboration is expected to increase consistency between studies by developing Inhibitors,research,lifescience,medical common methodologies, common measurement instruments, and correspondence between definitions of conversion. Several other networks have been initiated throughout Europe, including the European Prediction of Psychosis Study (EPOS) in Finland, led by Salokangas, and the Swiss Consortium currently headed by Simon. Such collaborations offer the hope that large databases will result, each with far more subjects and statistical power than possible for any study alone. Conclusions have thus far been Inhibitors,research,lifescience,medical elusive given the rarity of the prodromal state and the difficulty in ascertaining a substantial prodromal population. Large-scale collaborations offer the promise of generating a solid set

of generalizable conclusions about the prodrome, which are reliable, valid, and representative of a broad preschizophrenia population.53 Selected abbreviations and acronyms Org 27569 AD antidepressant AP antipsychotic CBT cognitive behavioral therapy CHR clinical high risk NBI needs-based intervention PACE Personal Assessment and Crisis Evaluation (program) PRIME Prevention through Risk Identification, Management, and Education (program) RAP Recognition and Prevention (program) SGAP second-generation antipsychotic SLP schizophrenia-like psychosis SPI specific preventive intervention Notes This research was supported in part by National Institute of Mental Health grant MH-61523 to Dr Cornblatt. We would like to thank Ruth Olsen for her help with many of the technical aspects of this manuscript.

Subjects in the TA-NIC vaccine trial were immunized with 4 doses over the first 8 weeks and then given a booster dose at 32 weeks. All subjects were encouraged to quit smoking after 12 weeks of the trial, and at 12 months, the quit rate in the highest-dose group significantly exceeded the control group (38% vs 8%).50 Based on these studies suggesting that high antibody titers correlate with smoking cessation, evaluation of nicotine conjugate vaccines are progressing Inhibitors,research,lifescience,medical and a phase Ilb/III trial was recently announced for NicQb.51 selleck chemical alcohol Alcohol dependence is a major cause of morbidity and mortality in the United States and throughout the world. Acute withdrawal Inhibitors,research,lifescience,medical from alcohol

is a serious medical condition which can precipitate adrenergic activation, seizures, or delirium tremens, the last condition leading to 15% mortality when untreated.52 Many medications have been evaluated for the treatment of alcohol dependence

in recent years, including those that interact with dopaminergic, serotonergic, opioid, glutamate, and γ-aminobutyric acid (GABA) systems. Acute withdrawal Benzodiazepine Inhibitors,research,lifescience,medical use is the standard approach to treating withdrawal symptoms such as irritability, autonomic hyperactivity, and seizures associated with alcohol detoxification. Benzodiazepines act at GABA-A receptors to stimulate GABA release and gradually detoxify the patient from alcohol, thus avoiding associated withdrawal symptoms.53 The current

standard approach to alcohol detoxification uses tapering dosages of benzodiazepines such as chlodiazepoxide, clonazepam, diazepam, oxazepam, or lorazepam.54,55 Anticonvulsants, including carbamazepine and valproate, have also been studied Inhibitors,research,lifescience,medical for their efficacy in alcohol withdrawal treatment.6 Carbamazepine has been widely used in alcohol withdrawal. Inhibitors,research,lifescience,medical Carbamazepine has demonstrated its superiority to placebo in the speed of onset to relieve alcohol withdrawal symptoms such as tremor, sweating, palpitations, sleep disturbances, depression, anxiety, and anorexia.56 Furthermore, studies have also demonstrated that higher success rates and reduction in withdrawal symptoms in patients treated with carbamazepine than with benzodiazepines.57-59 of Relapse prevention ami maintenance Disulfiram, acamprosate, oral naltrexone, and extended-release injectable naltrexone have FDA approval for the treatment of alcohol dependence. Disulfiram is the first agent to be approved for treatment of alcohol dependence and has been used for over 40 years. It acts as an alcohol-sensitizing agent, creating an aversion to alcohol. Disulfiram is an irreversible inhibitor of the enzymatic conversion of acetalaldehyde to acetic acid. Accumulation of acetalaldehyde results in the disulfiram-alcohol reaction: hypotension, flushing, nausea, and vomiting.