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PubMed2006

Pharmacological studies on fullerene (C60), a novel carbon allotrope, and its derivatives.

Fullerene (C(60)), a condensed ring aromatic compound with extended pi systems, is a novel carbon allotrope. Because of its poor solubility in polar solvents, investigation of the biological and pharmacological properties of fullerene has been difficult. Recently, water-soluble fullerene derivatives have been synthesized, and we and others have found that they have potent and selective pharmacological effects on organs, cells, enzymes, and nucleic acids. In the presence of fullerene C(60) derivative (10(-5) M), endothelium-dependent relaxations induced by agonists in the vascular system were eliminated and acetylcholine-induced contractile response of smooth muscle was observed. Some investigators have reported free radical-scavenging activity and direct nitric oxide-quenching activity of fullerene derivatives. Knowledge of the chemical modifications, biological significance, and materials applications of functionalized fullerenes is growing rapidly; and these compounds are emerging as new tools in the field. The focus of this review is to introduce several pharmacological effects of fullerenes and to discuss the possible mechanisms of the pharmacological actions caused by previously synthesized fullerenes.

Acetylcholine↗
PubMed2004

Pharmacologic perspectives for once-daily antiretroviral therapy.

OBJECTIVE: To contrast available once-daily antiretroviral agents and combinations of these agents from a clinical pharmacologic viewpoint. DATA SOURCES: Data were extracted from publications and major HIV conference proceedings cited in MEDLINE (1966-March 2004) using the search terms antiretroviral therapy, combination therapy, once-daily therapy, and pharmacokinetics. Additional references were obtained from the bibliographies of these sources. STUDY SELECTION AND DATA EXTRACTION: Information pertaining to pharmacologic perspectives for once-daily antiretroviral agents was selected. DATA SYNTHESIS: Maximal and durable suppression of plasma HIV RNA, the principal goal of therapy, depends on the intrinsic antiviral activity of the antiretroviral regimen. A favorable tolerability/toxicity profile is also fundamentally important. All once-daily agents exhibit some pharmacologic limitations or lack adequate long-term follow-up. Of available agents, efavirenz has a long and distinguished efficacy record, with reasonable safety and moderate tolerability. Lamivudine, and newer agents such as atazanavir (or atazanavir/ritonavir), emtricitabine, fosamprenavir/ritonavir, and tenofovir, may offer pharmacologic advantages in the current state of once-daily therapy. Important considerations exist for coadministering once-daily agents including drug-drug interactions, drug-food incompatibilities, and synergistic toxicities. Few controlled studies have compared once-daily regimens with conventional regimens. CONCLUSIONS: Progress has been made toward once-daily therapy, but more clinical experience with available agents is needed, including comparative studies of entirely once-daily regimens versus conventional regimens. Limitations of currently available agents signify a need for improved antiretroviral utilization or new alternative agents.

Anti-HIV Agents↗
PubMed2003

Pharmacological manipulation of glutamate transport.

L-Glutamic acid acts as the major excitatory neurotransmitter and, at the same time, represents a potential neurotoxin for the mammalian central nervous system (CNS). The termination of excitatory transmission and the maintenance of physiologic levels of extracellular glutamate, which is necessary to prevent excitotoxicity, are prominently mediated by a family of high-affinity sodium-dependent excitatory amino acid transporters (EAATs). Five subtypes of EAATs have been cloned, possessing distinct pharmacology, localization, sensitivity to transport inhibitors and modulatory mechanisms. Expression and activity of EAATs have been shown to be amenable to fine endogenous and, potentially, pharmacological regulation by substrate itself, growth factors, second messengers, hormones, biological oxidants, inflammatory mediators and pathological conditions. The present review describes basic pharmacological studies, mostly performed on animal models or cell preparations, in order to obtain an updated picture of the known regulatory mechanisms of single EAAT expression and activity. New insight into molecular pathways involved in EAAT regulation will allow pharmacological manipulation of excitatory CNS activity, possibly avoiding adverse effects of glutamate receptor blockade.

Amino Acid Transport System X-AG↗
PubMed2003

Non-pharmacological interventions in cognitively impaired and demented patients--a comparison with cholinesterase inhibitors.

The present paper reviews studies examining the effects of non-pharmacological stimulation, i.e. bright light, physical activity and tactile stimulation (touch), on cognition, affective behaviour, and the sleep-wake rhythm of impaired and demented elderly, both in a qualitative (narrative) and quantitative (meta-analytic) manner. An extensive search through eight bibliographic data bases (PubMed, Web of Science, ERIC, PsychINFO, Psyndex, Cinahl, Biological Abstracts and Rehabdata) was performed up to August 2002. The primary criterion for inclusion in this review was that studies provided sufficient data to calculate effect-sizes. In the qualitative analysis, all three types of stimulation appeared to improve cognitive functioning. Disturbances in behaviour react positively to bright light and tactile stimulation. Bright light was also beneficial to sleep. Tactile stimulation had, moreover, a beneficial influence on the patient-caretaker relationship. A comparison was made with several representative papers published since 1991 on the effects of acetylcholinesterase inhibitors on cognition and behaviour with representative papers on non-pharmacological stimulation interventions. Data indicated that improvements in cognition and affective behaviour by non-pharmacological interventions (d' = 0.32) and by cholinesterase inhibitors (d' = 0.31) were of similar effect-size. Possible mechanisms underlying the non-pharmacological stimulation effects are discussed and suggestions offered for future research.

Affect↗
PubMed2004

Drug-eluting stents: a mechanical and pharmacologic approach to coronary artery disease.

Coronary artery disease is the largest killer of men and women in the United States and costs the health care system billions of dollars annually. Several advances in both mechanical and pharmacologic treatment of coronary artery disease have occurred in recent decades. Mechanically, percutaneous coronary intervention is commonly used to treat coronary atherosclerosis. This approach has dramatically reduced both morbidity and mortality for patients with different levels of severity of coronary artery disease. However, percutaneous coronary intervention is limited by restenosis, which is an increase in growth of the intimal layer of the vessel wall. Despite the introduction of intracoronary stents and the addition of systemic pharmacotherapy, restenosis still affects a significant number of patients. The new technology of drug-eluting stents combines mechanical and pharmacologic approaches to prevent restenosis. Various types of these stents exist in different stages of development; several have been shown to prevent or reduce intimal growth after stent deployment. An understanding of how this combined mechanical and pharmacologic approach reduces restenosis requires consideration of complex issues in pathophysiology and pharmacology.

Angioplasty, Balloon, Coronary↗
PubMed1995

Pharmacological intervention in older patients with rheumatoid arthritis. Quality of life aspects.

Despite the rather pessimistic outlook regarding the long term effects of pharmacological treatment of patients with rheumatoid arthritis (RA), there is no doubt that drug interventions can affect quality of life (QOL). The disease has a significant impact upon physical, psychological and social function, and QOL optimisation should cover all these dimensions. Swelling of joints and pain are important manifestations in assessing RA since these may result in sleep disturbances as well as depressed mood. This might be particularly significant for older persons with RA. Outcome parameters of RA can be divided into short, intermediate and long term. The long term results are quite disappointing with regard to disability and premature death. However, more intermediate outcome measures related to QOL might improve after pharmacological interventions. Patient preferences and expectations with regard to the outcome of pharmacological interventions are important parameters to assess. When assessing older patients with RA with QOL instruments, it is recommended that questionnaires are fairly short and easy to complete. Adverse effects of pharmacological interventions are important factors to monitor in QOL assessment in older patients with reduced remaining life span.

Adverse Drug Reaction Reporting Systems↗
PubMed2006

Did the introduction of a prospective payment system for nursing home stays reduce the likelihood of pharmacological management of secondary ischaemic stroke?

BACKGROUND: Since 1998, a prospective payment system (PPS) for Medicare services provided by nursing homes in the US has been in operation. Concerns have been expressed that the PPS may affect the quality of care delivered to residents. This study evaluates the impact of the PPS on pharmacological secondary ischaemic stroke prevention in nursing homes. STUDY DESIGN: The nationally mandated Minimum Data Set and Online Survey Certification and Automated Record data system from 1997 and 2000 for four states were used. We conducted a quasi-experimental study comparing the pharmacological treatment rates for secondary stroke prevention in the pre-PPS period (1997) with those in the post-PPS period (2000) in residents who experienced an ischaemic stroke within 6 months (n1997 = 5008; n2000 = 5243) of living in nursing facilities (n1997 = 1226; n2000 = 1092) in Kansas, Maine, Mississippi or Ohio. The sample was stratified according to recommendations for use of warfarin. Logistic regression models adjusting for clustering effects of residents residing in homes using generalised estimating equations provided estimates of the PPS effect on use of antiplatelets and the use of warfarin. RESULTS: The unadjusted proportion of use of pharmacological agents for the secondary prevention of stroke was similar for warfarin in both time periods and increased for antiplatelets in 2000. Relative to the pre-PPS era, the likelihood of use of antiplatelets increased in the post-PPS era (adjusted odds ratio 1.26; 95% CI 1.15, 1.38); there was no effect on the use of warfarin. CONCLUSION: Although the lack of a PPS effect on pharmacological management of secondary ischaemic stroke is encouraging, there is still room for improvement in overall stroke management.

Aged↗
PubMed2005

Pharmacological management of overactive bladder : a systematic and critical review of published economic evaluations.

Overactive bladder is a common condition, with recent findings estimating the prevalence in adults at about 15%. Symptoms, including urinary urgency, high voiding frequency and urge incontinence, have been shown to decrease patients' quality of life. Given its high prevalence, the economic burden of overactive bladder is also substantial, with a recent estimate placing the annual cost in the US at 9.1 billion US dollars (year 2000 values). The objective of this review is to provide a critical appraisal of published economic evaluations of pharmacological and non-pharmacological treatments for overactive bladder. Published economic evaluations of treatments for overactive bladder have focused entirely on pharmacological treatments -- mainly on the two most commonly used drugs, oxybutynin and tolterodine, each of which is available in immediate- and extended-release formulations. Ten economic evaluations (more than half are cost-effectiveness studies) have been published. Modelling with decision trees or Markov models has been the predominant method. Evaluations comparing drug therapy with no treatment have concluded that drug therapy is cost effective. Analyses comparing the formulations of oxybutynin and tolterodine have produced highly inconsistent results, largely due to the sources of data employed for effectiveness and treatment discontinuation rates. There are no evaluations of drugs relative to non-pharmacological treatment, and there are other significant gaps in the economic evaluations of treatment to date. These include gaps resulting from a lack of reliable data on the performance of these drugs in real-world settings, particularly data on long-term persistence with treatment. A more definitive pharmacoeconomic comparison of oxybutynin and tolterodine formulations, incorporating all available clinical data, and other treatment options would help direct treatment.

Benzhydryl Compounds↗
PubMed2005

Dopamine-glutamate interaction and antipsychotics mechanism of action: implication for new pharmacological strategies in psychosis.

Schizophrenia is a severe mental illness characterized by behavioral and cognitive symptoms. Several lines of evidence focus on a direct involvement of the glutamatergic system in the pathophysiology of psychosis. The hypofunction of the ionotropic glutamate N-methyl-D-Aspartate Receptor (NMDA-R) has been proposed as a model of schizophrenia in humans. Cortical and subcortical glutamate release seems to be modulated by dopaminergic and, to a lesser extent, serotoninergic circuitries, and tuned by intracellular pathways. Although dopamine D(2) receptor blockade is a crucial mechanism of antipsychotics pharmacodynamic profile, a putative glutamatergic impact of these compounds is suggested by animal pharmacological isomorphisms of psychosis as well as by clinical studies. According to this view, the balance between D(2) antagonism and NMDA-R modulation may be pivotal for the improvement of both positive and negative symptoms. Recently, many pharmacological strategies involving glutamate receptors have been suggested, and novel compounds and pharmacological strategies acting on glutamate transmission are currently under evaluation: i) augmentation strategies improving NMDA-R transmission (glycine, D-serine, D-cycloserine, glycine transporter inhibitors); ii) ampakines, positive modulators of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptor complex; iii) agonists of glutamate metabotropic receptors; iv) drugs involved in subcellular adaptation both at pre- and post-synaptic sites. Furthermore, molecular markers, suggesting modulation of glutamate circuitries after antipsychotics administration, are an attractive tool to shed more light on glutamate involvement in antipsychotics mechanism of action. In this review we provide a critical update of recent preclinical and clinical data on dopamine-glutamate interaction and its role in new pharmacological strategies for psychosis treatment.

Animals↗
PubMedDate not supplied

Biological and pharmacological approaches to the screening and evaluation of natural products.

Many traditional herbal remedies contain active principles, the effects of which can be demonstrated pharmacologically; the biological activity of the whole plant extract is usually related to the constituents that have been identified. Thus, active extracts detected by screening methods are often subjected to more elaborate bioassays to determine their specific pharmacological activity. This paper aims to elucidate the biological, pharmacological and clinical approaches used in the screening of bioactive natural substances. In addition, a scientific process with the goal of finding substances with useful pharmacological activity in plant extracts is rigorously investigated.

Biological Assay↗
PubMed1987

The pharmacological treatment of tricyclic-resistant depression: review and management guidelines.

Despite the introduction of a wide range of antidepressant drugs since the late 1950s, approximately 30-50% of depressed subjects do not respond to these agents. Various treatment strategies, both pharmacological and non-pharmacological, have been proposed for treatment-resistant depression. This paper critically reviews the studies of single and combined pharmacological treatments for tricyclic-resistant patients, with a particular discussion of lithium augmentation. The major inadequacies of these studies have been the frequent lack of definitions of treatment resistance, the heterogeneity of the depressed samples, and the infrequent use of double-blind, placebo-controlled designs. Two central issues, definition of treatment resistance and clinical predictors of response to pharmacological treatments, are discussed in detail. Finally, a suggested guideline for the management of tricyclic-resistant depression is proposed.

Antidepressive Agents↗
PubMedDate not supplied

Pharmacological advances in addiction treatment.

In the past 20 years significant advances in the pharmacological treatment of opioid dependence have been made, and research in this area is continuing. Therapeutic applications and current research in the use of pharmacological agents in maintenance therapy, treatment with narcotic antagonists, and narcotic detoxification are discussed. In addition, an overview is presented of recent developments in opioid pharmacology and of recently developed novel pharmacological agents which may prove useful in the future treatment and/or prevention of opioid dependence.

Benzodiazepines↗
PubMed2006

A systematic literature review of the effectiveness of non-pharmacological interventions to prevent wandering in dementia and evaluation of the ethical implications and acceptability of their use.

OBJECTIVES: To determine the effectiveness and cost-effectiveness of non-pharmacological interventions (excluding subjective barriers) in the prevention of wandering in people with dementia, in comparison with usual care, and to evaluate through the review and a qualitative study the acceptability to stakeholders of such interventions and identify ethical issues associated with their use. DATA SOURCES: Major electronic databases were searched up until 31 March 2005. Specialists in the field. REVIEW METHODS: Selected studies were assessed and analysed. The results of two of the efficacy studies that used similar interventions, designs and outcome measures were pooled in a meta-analysis; results for other studies which reported standard deviations were presented in a forest plot. Owing to a lack of cost-effectiveness data, a modelling exercise could not be performed. Four focus groups were carried out with relevant stakeholders (n = 19) including people with dementia and formal and lay carers to explore ethical and acceptability issues in greater depth. Transcripts were coded independently by two reviewers to develop a coding frame. Analysis was via a thematic framework approach. RESULTS: Ten studies met the inclusion criteria (multi-sensory environment, three; music therapy, one; exercise, one; special care units, two; aromatherapy, two; behavioural intervention, one). There was no robust evidence to recommend any non-pharmacological intervention to reduce wandering in dementia. There was some evidence, albeit of poor quality, for the effectiveness of exercise and multi-sensory environment. There were no relevant studies to determine the cost-effectiveness of the interventions. Findings from the narrative review and focus groups on acceptability and ethical issues were comparable. Exercise and distraction therapies were the most acceptable interventions and raised no ethical concerns. All other interventions were considered acceptable except for physical restraints, which were considered unacceptable. Considerable ethical concerns exist with the use of electronic tagging and tracking devices and physical barriers. Existing literature ignores the perspectives of people with dementia. The small number of participants with dementia expressed caution regarding the use of unfamiliar technology. Balancing risk and risk assessment was an important theme for all carers in the management of wandering. CONCLUSIONS: There is no robust evidence so far to recommend the use of any non-pharmacological intervention to reduce or prevent wandering in people with dementia. High-quality studies, preferably randomised controlled trials, are needed to determine the clinical and cost-effectiveness of non-pharmacological interventions that allow safe wandering and are considered practically and ethically acceptable by carers and people with dementia. Large-scale, long-term cohort studies are needed to evaluate the morbidity and mortality associated with wandering in dementia for people both in the community and in residential care. Such data would inform future long-term cost-effectiveness studies.

Confusion↗
PubMed2004

The quality of pharmacologic care for vulnerable older patients.

BACKGROUND: Although pharmacotherapy is critical to the medical care of older patients, medications can have considerable toxicity in this age group. To date, research has focused on inappropriate prescribing and policy efforts have aimed at access, but no comprehensive measurement of the quality of pharmacologic management using explicit criteria has been performed. OBJECTIVE: To evaluate the broad range of pharmacologic care processes for vulnerable older patients. DESIGN: Observational cohort study. SETTING: 2 managed care organizations enrolling older persons. PATIENTS: Community-dwelling high-risk patients 65 years of age or older continuously enrolled in the managed care organizations from 1 July 1998 to 31 July 1999. MEASUREMENTS: Patients' receipt of care as specified in 43 quality indicators covering 4 domains of pharmacologic care: 1) prescribing indicated medications; 2) avoiding inappropriate medications; 3) education, continuity, and documentation; and 4) medication monitoring. RESULTS: Of 475 vulnerable older patients, 372 (78%) consented to participate and had medical records that could be abstracted. The percentage of appropriate pharmacologic management ranged from 10% for documentation of risks of nonsteroidal anti-inflammatory drugs to 100% for avoiding short-acting calcium-channel blockers in patients with heart failure and avoiding beta-blockers in patients with asthma. Pass rates for quality indicators in the "avoiding inappropriate medications" domain (97% [95% CI, 96% to 98%]) were significantly higher than pass rates for "prescribing indicated medications" (50% [CI, 45% to 55%]); "education, continuity, and documentation" (81% [CI, 79% to 84%]); and "medication monitoring" (64% [CI, 60% to 68%]). LIMITATIONS: Fewer than 10 patients were eligible for many of the quality indicators measured, and the generalizability of these findings in 2 managed care organizations to the general geriatric population is uncertain. CONCLUSIONS: Failures to prescribe indicated medications, monitor medications appropriately, document necessary information, educate patients, and maintain continuity are more common prescribing problems than use of inappropriate drugs in older patients.

Aged↗
PubMed1999

Postnatal development of hippocampal dentate granule cell gamma-aminobutyric acidA receptor pharmacological properties.

Postnatal development of hippocampal dentate granule cell gamma-aminobutyric acidA (GABAA) receptor pharmacological properties was studied. Granule cells were acutely isolated from hippocampi of 7- to 14- and 45- to 52-day-old rats, and whole cell patch-clamp recordings were obtained. The sensitivity of GABAA receptors to GABA and modulation of GABAA receptor currents by benzodiazepines (BZ), zinc, furosemide, and loreclezole was studied. Multiple changes in the pharmacological properties of dentate granule-cell GABAA receptors occurred during the first 52 days of postnatal development: GABA-evoked maximal current increased with postnatal age; GABAA receptors changed from BZ type 3 in young rats to BZ type 1 in adult rats; furosemide and zinc inhibited GABAA receptor currents in young rats but not in adult rats; the fraction of cells that expressed loreclezole-sensitive GABAA receptors increased with postnatal age. These findings suggest that dentate granule cells in young and adult animals express pharmacologically distinct GABAA receptors and that the postnatal development of these receptors is prolonged, lasting at least 45 days. Comparison with the previously reported pharmacological properties of GABAA receptors on dentate granule cells acutely isolated from hippocampi of 28- to 35-day-old rats suggests that receptors expressed at that age have properties intermediate between young and adult rats.

Animals↗
PubMed1998

The efficacy and safety of a pharmacologic protocol for maintaining coronary artery bypass patients at a higher mean arterial pressure during cardiopulmonary bypass.

A recent randomized trial of higher versus lower mean arterial pressure (MAP) during cardiopulmonary bypass (CPB) showed that higher MAP on CPB was associated with a lower incidence of overall cardiac and neurologic morbidity and mortality in coronary artery bypass graft surgery (CABG) patients. Cardiopulmonary bypass MAP was controlled pharmacologically while CPB flow was held constant for any given period. The objective of the present study was to assess the efficacy and safety of this pharmacologic protocol. Two hundred forty-eight patients participated in the study; the mean age was 65.8 +/- 9.4 years, 20% were women, and the mean preoperative ejection fraction was 48%. The low-flow corrected CPB MAP attained for the low and high MAP groups was 56.7 +/- 5.0 mmHg and 77.7 +/- 7.1 mmHg, respectively (p = 0.0001). Major cardiac and neurologic outcomes, postoperative blood loss, renal dysfunction, intensive care unit (ICU) stay, and duration of intubation were not found to be significantly associated with any drug in the pharmacologic protocol. These findings support that the pharmacologic protocol used to maintain CABG patients at higher MAP on CPB is both efficacious and safe.

Aged↗
PubMed1999

Expression of the GLT-1 subtype of Na+-dependent glutamate transporter: pharmacological characterization and lack of regulation by protein kinase C.

Several subtypes of Na+-dependent glutamate transporters have been pharmacologically differentiated in brain tissues. Five distinct cDNA clones that express Na+-dependent glutamate transport activity have been isolated. One goal of the current study was to compare the pharmacological properties of the rat GLT-1 subtype of transporter to those identified previously using rat brain tissues. To accomplish this goal, GLT-1 was stably transfected into two different cell lines that express low levels of endogenous transport activity (MCB and L-M (TK-)). Several clones stably transfected with GLT-1 were isolated. In each cell line, Na+-dependent glutamate transport activity was saturable with similar Km values (19 and 37 microM). The pharmacological properties of GLT-1-mediated transport in these cell lines paralleled those observed for the predominant pharmacology observed in cortical crude synaptosomes. These data are consistent with other lines of evidence that suggest that GLT-1 may be sufficient to explain most of the Na+-dependent glutamate transport activity in cortical synaptosomes. Although recent studies using HeLa cells have suggested that GLT-1 can be rapidly up-regulated by activation of protein kinase C (PKC), modulation of PKC or phosphatase activity had no effect on GLT-1-mediated activity in these transfected cell lines. To determine if GLT-1 regulation by PKC is cell-specific, HeLa cells, which endogenously express the EAAC1 subtype of transporter, were stably transfected with GLT-1. Although EAAC1-mediated activity was increased by activation of PKC, we found no evidence for regulation of GLT-1. Despite the present findings, GLT-1 activity may be regulated by PKC under certain conditions.

ATP-Binding Cassette Transporters↗
PubMed1999

Pharmacologic and pharmacokinetic considerations in choosing an antipsychotic.

Recent advances in our understanding of schizophrenia along with neuroscience insights into antipsychotic medication mechanisms of action have led to a renaissance in new drug development, including an expanded therapeutic spectrum encompassing more of the symptoms encountered in schizophrenia. Atypical antipsychotics, or new generation therapies, also demonstrate greater selectivity for therapeutic actions than for extrapyramidal symptoms (EPS). Our modern armamentarium of drugs spans a wide range of pharmacologies, and it is more accurate to envision shades of gray rather than a black-and-white description for typical versus atypical properties of medications. As our paradigms for antipsychotic efficacy have shifted, a reexploration of the "older" neuroleptics is warranted to determine if they possess pharmacologic attributes that might have been overlooked during the era of high-dose neuroleptic therapy. Loxapine appears to be in the center of this spectrum, somewhere between haloperidol and risperidone. Dosing implications for drugs with a more even serotonin-2A (5-HT2A) receptor and dopamine-2 (D2) receptor blocking effect are discussed. Loxapine might have a window of partial atypicality at doses < or = 50 mg/day. These lower doses might have potential as both monotherapy in responsive patients with persistent psychotic disorders and as an adjunctive treatment in partially responding patients on concurrent atypical antipsychotic treatments. The pharmacologic properties of loxapine within its usable dosage range are quite complex and are the net sum of the parent's plus metabolites' contributions (demethylation and hydroxylation by cytochrome P450 enzymes). These pharmacologic effects include alpha-adrenergic blockade, inhibition of the noradrenergic transporter protein (reuptake inhibition), and antimuscarinic effects. Drug interactions and cigarette smoking might alter the parent-to-metabolite concentration ratios, affecting the relative atypicality of this antipsychotic therapy. Moreover, with the intramuscular formulation, which does not undergo first-pass metabolism, the parent compound of loxapine, i.e., not its metabolites, is predominantly detected in the plasma of patients, reducing the likelihood for EPS during emergency interventions in patients with positive symptoms. Further study is warranted to determine loxapine's place in our treatment of schizophrenia.

Antipsychotic Agents↗