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Biomedical subjects

David H Adams

Publications and source records attributed to David H Adams.

At least 37 records · Page 2Linked to original sources
PubMed2006

A 24-week randomized study of olanzapine versus ziprasidone in the treatment of schizophrenia or schizoaffective disorder in patients with prominent depressive symptoms.

OBJECTIVE: The objective of this study is to compare olanzapine with ziprasidone therapy in patients with schizophrenia or schizoaffective disorder and experiencing depressive symptoms. METHODS: This randomized, double-blind, 24-week, fixed-dose study compared olanzapine (n = 202) and ziprasidone (n = 192) for patients with schizophrenia or schizoaffective disorder and experiencing prominent depressive symptoms. Outcome measures included change in Calgary Depression Scale for Schizophrenia (CDSS) score from baseline to 8 weeks (primary outcome) and changes in CDSS, Montgomery-Asberg Depression Rating Scales, Positive and Negative Syndrome Scale, and Global Assessment of Functioning (GAF) scores for 24 weeks. Statistical analyses included mixed-effects model repeated measures (primary analysis) and change from baseline to last observation carried forward (LOCF). RESULTS: At baseline, patients had moderate depressive symptoms (mean Montgomery-Asberg Depression Rating Scales total score, 27.3). For 8 weeks, patients treated with olanzapine or ziprasidone had significant improvements on CDSS. Treatment group differences were not statistically significant (P = 0.493, mixed-effects model repeated measures; P = 0.497, LOCF). For 24 weeks, olanzapine-treated patients showed significantly greater improvements in depressive symptoms (results varied by depression measure and statistical approach) and GAF (P < 0.017, LOCF). A significantly higher proportion of olanzapine-treated patients completed the study (44.6% vs 29.7%; P = 0.003) and remained longer on medication (median, 163 vs 73 days, P < 0.001), compared with ziprasidone-treated patients. Olanzapine-treated patients experienced significantly (P < 0.05) greater increases in triglycerides, HgbA1c, and weight. CONCLUSIONS: For 24 weeks, olanzapine-treated patients had greater and more sustained participation in treatment, during which time significantly greater improvements were observed in depressive symptoms and GAF scores, along with increases in weight and certain metabolic parameters as compared with ziprasidone-treated patients.

Antipsychotic Agents↗
PubMed2006

Differential rates of treatment discontinuation in clinical trials as a measure of treatment effectiveness for olanzapine and comparator atypical antipsychotics for schizophrenia.

Antipsychotic treatment discontinuation can be used to measure overall treatment effectiveness. Our goal was to investigate differential treatment discontinuation comparing olanzapine with other atypical antipsychotics. A post hoc pooled analysis of 4 randomized, double-blind, 24- to 28-week schizophrenia clinical trials included 822 olanzapine-treated and 805 risperidone-, quetiapine-, or ziprasidone-treated patients. A checklist was used to record the reason for discontinuation. Treatment differences were assessed between olanzapine and the other 3 antipsychotics combined. Poor response/symptom worsening was the primary reason for discontinuation, regardless of medication. The rate of discontinuation due to poor response/symptom worsening significantly varied by treatment (olanzapine, 14.23%, vs. other atypical antipsychotics, 24.60%; P < 0.0001). The rate of discontinuation due to intolerability of medication did not significantly vary by treatment (olanzapine, 5.60%, vs. other atypical antipsychotics, 7.45%; P = 0.13). Consequent to the differential rates of discontinuation due to poor response/symptom worsening, the olanzapine-treated patients experienced a significantly greater likelihood of overall treatment completion (53.9% vs. 39.3%; P < 0.001) and a significantly longer duration of treatment (19.1 vs. 16.1 weeks; P < 0.0001) than other atypical-treated patients. The predominant reason for the significantly lower discontinuation rate of treatment for patients taking olanzapine compared with that of patients taking other atypical antipsychotics was the significantly higher dropout rates in other atypical antipsychotics because of poor response/symptom worsening.

Adult↗
PubMed2006

Physiologic basis for the surgical treatment of ischemic mitral regurgitation.

Ischemic mitral regurgitation (MR) can complicate severe coronary artery disease and myocardial infarction. Ischemic MR results from left ventricular remodeling after myocardial infarction and can also accompany acute myocardial ischemia. The most common mechanism of ischemic MR is Carpentier's type IIIb dysfunction due to an apical and lateral displacement of papillary muscles leading to a tethering of the mitral leaflets. This apical tenting of the leaflets prevents the free margin from reaching the plane of the annulus, significantly reduces the surface of coaptation, and causes MR. Recent advances in imaging studies have led to a better understanding of the pathophysiology of this condition as well as to the development of innovative surgical approaches to treat this disease. Current research efforts have mainly focused on 2 directions: (1) percutaneous approaches to correct MR, and (2) surgical therapy to address the ventricular component of the disease. In this article, the authors define ischemic MR and review its pathophysiology, current management strategies, and future directions.

Clinical Trials as Topic↗
PubMed2006

Expression of DC-SIGN and DC-SIGNR on human sinusoidal endothelium: a role for capturing hepatitis C virus particles.

Hepatic sinusoidal endothelial cells are unique among endothelial cells in their ability to internalize and process a diverse range of antigens. DC-SIGNR, a type 2 C-type lectin expressed on liver sinusoids, has been shown to bind with high affinity to hepatitis C virus (HCV) E2 glycoprotein. DC-SIGN is a closely related homologue reported to be expressed only on dendritic cells and a subset of macrophages and has similar binding affinity to HCV E2 glycoprotein. These receptors function as adhesion and antigen presentation molecules. We report distinct patterns of DC-SIGNR and DC-SIGN expression in human liver tissue and show for the first time that both C-type lectins are expressed on sinusoidal endothelial cells. We confirmed that these receptors are functional by demonstrating their ability to bind HCV E2 glycoproteins. Although these lectins on primary sinusoidal cells support HCV E2 binding, they are unable to support HCV entry. These data support a model where DC-SIGN and DC-SIGNR on sinusoidal endothelium provide a mechanism for high affinity binding of circulating HCV within the liver sinusoids allowing subsequent transfer of the virus to underlying hepatocytes, in a manner analogous to DC-SIGN presentation of human immunodeficiency virus on dendritic cells.

Cell Adhesion Molecules↗
PubMed2006

Differential efficacy of olanzapine and lithium in preventing manic or mixed recurrence in patients with bipolar I disorder based on number of previous manic or mixed episodes.

INTRODUCTION: Bipolar disorder outcome worsens as number of manic episodes increases, suggesting that prevention of recurrent episodes early during the disorder could improve patient prognosis. We investigated treatment efficacy in prevention of mood episodes in patients subgrouped by number of prior manic episodes. METHOD: This study was a post hoc analysis of data from a multicenter, double-blind, 12-month clinical trial of relapse/recurrence in 431 initially euthymic patients with at least 2 prior manic/ mixed episodes and a DSM-IV diagnosis of bipolar I disorder randomly assigned to olanzapine (5-20 mg/day) or lithium (serum concentration 0.6 to 1.2 mEq/L). Data were collected between August 1999 and June 2002. Patients were subcategorized by illness stage according to number of prior manic/mixed episodes-early stage: 2 prior episodes (N = 53, lithium; N = 48, olanzapine), intermediate stage: 3 to 5 prior episodes (N = 80, lithium; N = 98, olanzapine), and later stage: more than 5 prior episodes (N = 81, lithium; N = 71, olanzapine)-and were evaluated for rates of relapse/recurrence. RESULTS: There were significant effects for treatment (p < .001) and illness stage (p = .006) but no significant interaction (p = .107) on rate of manic/mixed relapse/recurrence. Rates of manic/ mixed relapse/recurrence for olanzapine versus lithium were 2.1% versus 26.4% (p = .008), 13.3% versus 23.8% (p = .073), and 23.9% versus 33.3% (p = .204) for early-, intermediate-, and later-stage groups, respectively. There was no significant effect for treatment (p = .096) or illness stage (p = .731) for depressive relapse/recurrence. CONCLUSIONS: Early-stage (but not intermediate-or later-stage) patients had a significantly lower rate of relapse/recurrence of manic/mixed episodes with olanzapine compared to lithium. Thus, olanzapine maintenance therapy may be particularly effective early in the course of bipolar illness.

Adult↗
PubMed2006

A 7-week, randomized, double-blind trial of olanzapine/fluoxetine combination versus lamotrigine in the treatment of bipolar I depression.

OBJECTIVE: Determine the efficacy and tolerability of olanzapine/fluoxetine combination (OFC) for treatment of acute bipolar I depression compared with lamotrigine. METHOD: The 7-week, acute phase of a randomized, double-blind study compared OFC (6/25, 6/50, 12/25, or 12/50 mg/day; N = 205) with lamotrigine ([LMG] titrated to 200 mg/day; N = 205) in patients with DSM-IV-diagnosed bipolar I disorder, depressed. The study was conducted from November 2003 to August 2004. RESULTS: Completion rates were similar between treatments (OFC, 66.8% vs. LMG, 65.4%; p = .835). OFC-treated patients had significantly greater improvement than lamotrigine-treated patients in change from baseline across the 7-week treatment period on the Clinical Global Impressions-Severity of Illness scale (primary outcome) (p = .002, effect size = 0.26), Montgomery-Asberg Depression Rating Scale (MADRS) (p = .002, effect size = 0.24), and Young Mania Rating Scale total scores (p = .001, effect size = 0.24). Response rates did not significantly differ between groups when defined as > or = 50% reduction in MADRS score (OFC, 68.8% vs. LMG, 59.7%; p = .073). Time to response was significantly shorter for OFC-treated patients (median days [95% CI] = OFC, 17 [14 to 22] vs. LMG, 23 [21 to 34]; p = .010). There was a significant difference in incidence of "suicidal and self-injurious behavior" adverse events (OFC, 0.5% vs. LMG, 3.4%; p = .037). Somnolence, increased appetite, dry mouth, sedation, weight gain, and tremor occurred more frequently (p < .05) in OFC-treated patients than lamotrigine-treated patients. Weight, total cholesterol, and triglyceride levels were significantly elevated in OFC-treated patients compared with lamotrigine-treated patients (all p < or = .001). CONCLUSIONS: Patients with acute bipolar I depression had statistically significantly greater improvement in depressive and manic symptoms, more treatment-emergent adverse events, greater weight gain, and some elevated metabolic factors with OFC than lamotrigine. Treatment differences were of modest size.

Adult↗
PubMed2006

Outcomes and predictors of success of a radiofrequency- or cryothermy-simplified left-sided maze procedure in patients undergoing mitral valve surgery.

BACKGROUND AND AIM OF THE STUDY: Restoration of sinus rhythm with a maze procedure after concomitant mitral valve (MV) surgery has been shown to reduce the rate of stroke and improve cardiac function and quality of life compared to MV surgery alone. Unlike the classical Cox-Maze III operation, a simplified left-sided maze procedure can be performed without any significant increase in operative complexity. METHODS: Outcomes were compared retrospectively between radiofrequency (RF) and cryothermy as an energy source and analyzed predictors of outcome in 73 consecutive patients undergoing MV surgery with a concomitant simplified left-sided maze procedure. Clinical characteristics as well as rhythm and complication rate at follow up were assessed by review of medical records and patient and physician interview. RESULTS: There were no complications associated directly with the maze procedure. At an average follow up of 342 days, 69% of patients were in normal sinus rhythm. Of the remainder, 30% had recurrent atrial fibrillation (AF) and 1% atrial flutter. In addition, 7% of patients required cardioversion and 14% required anti-arrhythmic therapy to maintain sinus rhythm. Patients with recurrent AF were more likely to have an enlarged right atrium or Carpentier Type IIIa mitral regurgitation on preoperative echocardiography, and more likely to have undergone concomitant aortic or tricuspid valve surgery. There was no difference in outcome between RF and cryothermy as an energy source in unadjusted or adjusted analyses. CONCLUSION: The results of the study helped to establish RF- or cryothermy-simplified left-sided maze procedure as being efficacious and without associated complications in patients having MV surgery and a history of AF. Further investigations are warranted to better define the clinical predictors of recurrent AF to improve patient selection and potentially to modify current maze techniques.

Aged↗
PubMed2006

The modern surgical management of atrial fibrillation.

Atrial fibrillation is the most common arrhythmia disorder. Its incidence is especially high among patients with valvular heart disease. Patients with atrial fibrillation are at a six-fold increased risk of stroke and a two-fold increased risk of mortality. Medical management for rhythm control of patients with atrial fibrillation is suboptimal and no better than simple rate management. However, catheter-based therapies are undergoing intense development. The surgical management of atrial fibrillation has undergone considerable innovation in the last two decades; it is the subject of this review. The "cut-and-sew" Cox-maze III is considered the standard for surgical therapy for atrial fibrillation. More recently, several modifications of the Cox maze lesion set and the development of alternative energy sources to achieve transmural atrial lesions have led to a more simplified maze procedure. This simplified left-sided maze procedure has demonstrated excellent efficacy at intermediate and long-term follow-up. Therefore, the modified maze procedure should be offered to all mitral valve surgery patients and potentially to all cardiac surgery patients with a history of paroxysmal, persistent, or permanent atrial fibrillation.

Atrial Fibrillation↗
PubMed2006

Surgical management of functional tricuspid regurgitation with a new remodeling annuloplasty ring.

BACKGROUND: Moderate-to-severe functional tricuspid regurgitation (TR) should be corrected in patients undergoing surgery for left-sided valvular diseases, to improve long-term outcomes. Several techniques of surgical repair (suture annuloplasty or prosthetic annuloplasty) to correct this condition have been described. Multiple clinical studies have shown the superiority of prosthetic remodeling annuloplasty over the other surgical approaches. Despite this, suture-based annuloplasty remains the most commonly used technique for tricuspid valve repair. A new 3-dimensional remodeling prosthesis has been developed to address the issue of residual TR. We report our early experience with this new 3-dimensional prosthetic remodeling ring, the Edwards MC 3 system. MATERIAL: From August 2002 to March 2004, 51 patients (24 male, 27 female, mean age 64 +/- 15, ejection fraction 49 +/- 15, median NYHA III [II-IV]) underwent tricuspid valve repair for functional TR due to annular dilatation, with the Edwards MC 3 system. Etiology of left-sided valvular disease was: rheumatic (n = 19), degenerative (n = 16), ischemic cardiomyopathy (n = 1), and endocarditis (n = 5). Twenty (50%) patients underwent redo operations. Concomitant procedures included: mitral valve surgery (repair n = 34, replacement n = 14), aortic valve replacement (n = 5), coronary artery bypass graft (n = 8) and left arterial maze (n = 16). Median EuroSCORE was 12% (1-74%) in this patient population. RESULTS: Operative and late mortality were 3.8% (n = 2) and 13.7% (n = 7), respectively. Echocardiography at discharge showed a mean TR decrease from 3.1 +/- 0.9 to 0.3 +/- 0.4 (p < 0.001) and mean mitral regurgitation (MR) decrease from 3.2 +/- 1 to 0.1 +/- 0.1 (p < 0.001), while ejection fraction increased to 53% (p = 0.047), and at 6-month follow-up, mean TR and MR remained unchanged. CONCLUSION: Concomitant tricuspid valve repair for functional TR with left-sided valve surgery carries a low operative mortality. The Edwards MC 3 annuloplasty system is relatively simple to implant and corrects TR effectively (without significant residual TR), while providing excellent short-term clinical results. The 3-dimensional saddle shape of this ring may further optimize the fixation of the annulus in systolic position, and improve long-term results. Larger clinical series with longer-term follow-up are necessary to confirm these early promising results.

Aged↗
PubMed2005

Discontinuation of treatment of schizophrenic patients is driven by poor symptom response: a pooled post-hoc analysis of four atypical antipsychotic drugs.

BACKGROUND: Stopping antipsychotic treatment can interrupt improvement and exacerbate the illness. The reasons for discontinuing treatment during controlled clinical trials were analyzed to explore this phenomenon. METHODS: A post-hoc, pooled analysis was made of 4 randomized, double-blind clinical trials, 24-28 weeks in duration, involving 1627 patients with schizophrenia or a related disorder. Analyses combined all the atypical antipsychotic treatment groups in the studies. RESULTS: The majority of patients (53%) stopped their treatment at an early stage. Poor psychiatric response along with worsening symptoms was the most frequently given reason for discontinuing the course (36%), which was substantially more common than discontinuation due to poor tolerability of the medication (12%). This phenomenon was corroborated by less improvement in patients who discontinued treatment compared with those who completed, based on the PANSS total scores. Discontinuation due to poor response was, apparently, more predominantly linked to patient perception than to physicians' conclusions alone (80% vs. 20%). Discontinuation due to patient perception of poor response appeared to occur particularly early in the course of treatment. Patients who discontinued due to poor toleration of the medication responded in a more comparable manner with completers. CONCLUSION: Discontinuing treatment may lead to exacerbation of symptoms, undermining therapeutic progress. In these studies, poor response to treatment and worsening of underlying psychiatric symptoms, and to a lesser extent, intolerability to medication were the primary contributors to treatment being discontinued. Our findings suggest that adherence may be enhanced by effective symptom control, as objectively measured and as subjectively perceived. Such strategies may improve patients' willingness to undertake long-term therapy and increase the likelihood of a better prognosis.

Adult↗
PubMed2005

LSECtin interacts with filovirus glycoproteins and the spike protein of SARS coronavirus.

Cellular attachment factors like the C-type lectins DC-SIGN and DC-SIGNR (collectively referred to as DC-SIGN/R) can augment viral infection and might promote viral dissemination in and between hosts. The lectin LSECtin is encoded in the same chromosomal locus as DC-SIGN/R and is coexpressed with DC-SIGNR on sinusoidal endothelial cells in liver and lymphnodes. Here, we show that LSECtin enhances infection driven by filovirus glycoproteins (GP) and the S protein of SARS coronavirus, but does not interact with human immunodeficiency virus type-1 and hepatitis C virus envelope proteins. Ligand binding to LSECtin was inhibited by EGTA but not by mannan, suggesting that LSECtin unlike DC-SIGN/R does not recognize high-mannose glycans on viral GPs. Finally, we demonstrate that LSECtin is N-linked glycosylated and that glycosylation is required for cell surface expression. In summary, we identified LSECtin as an attachment factor that in conjunction with DC-SIGNR might concentrate viral pathogens in liver and lymph nodes.

Base Sequence↗
PubMed2005

CD40 mediated human cholangiocyte apoptosis requires JAK2 dependent activation of STAT3 in addition to activation of JNK1/2 and ERK1/2.

CD40 is critically involved in Fas-mediated cholangiocyte apoptosis during liver inflammation, but the underlying signalling events are poorly understood. Our recent work implicated AP-1 in CD40-induced cholangiocyte apoptosis, but suggested involvement of other signalling pathways. Because STAT3 has been implicated in liver regeneration we investigated this signalling pathway during CD40 mediated cholangiocyte apoptosis. Western immunoblotting, electrophoretic mobility gel shift assays, In situ DNA end labelling and caspase-3 activity were used to investigate intracellular signalling and apoptosis in primary human cholangiocytes following CD40 activation. CD40-activation induced caspase-3 dependent cholangiocyte apoptosis and 3-fold increases in JNK/ERK phosphorylation (concomitant with increased AP-1 binding activity) and 4-fold increases in pSTAT3, which were sustained for up to 24 h. Protein levels of c-Jun, c-Fos and pSTAT3 confirmed the upregulation. Phosphorylation of p38 remained unchanged suggesting that this MAP kinase was not involved in CD40 mediated apoptosis. Increased JAK2 phosphorylation accompanied increased STAT3 phosphorylation after CD40 ligation. Cholangiocytes were also shown to express JAK1 and 3 which was phosphorylated following control stimulation with TNFalpha or IL2 respectively but not after CD40 ligation. JNK, ERK and JAK2 inhibitors partially abrogated apoptosis and when used in combination reduced it to basal levels. In conclusion, induction of CD40-mediated cholangiocyte apoptosis requires JAK2-mediated phosphorylation of STAT3 as well as sustained JNK1/2, ERK1/2 activation. This study demonstrates that STAT3 can function as a proapoptotic factor in primary human liver epithelial cells.

Adenine↗
PubMed2005

A study of the metabolites of ischemia-reperfusion injury and selected amino acids in the liver using microdialysis during transplantation.

BACKGROUND: Preservation and ischemia-reperfusion injury still impact the outcome of orthotopic liver transplantation. The authors used microdialysis with a view to monitoring its effect on graft function. METHODS: A microdialysis catheter was inserted into the graft immediately after reperfusion and perfused with an isotonic solution for 48 hr. Metabolites of the ischemia-reperfusion injury and selected amino acids were studied. There were 18 patients, with a median age of 52 years (range, 38-62 years), 8 of whom were men. Lactate, pyruvate, glycerol, and glucose levels were measured. In addition, alanine, arginine, citrulline, gamma-aminobutyric acid (GABA), glutamate, glutamine, glycine, and taurine were determined. RESULTS: All grafts functioned well. High lactate, pyruvate, and glycerol levels were observed in the immediate postoperative period. These showed a significant rapid decrease and stabilized to baseline levels. Alanine, glutamate, GABA, and taurine levels declined significantly to baseline values. Arginine levels were low immediately postreperfusion and then increased, reaching significantly higher values beyond 19 hr. CONCLUSIONS: These data may represent "normal" changes seen in the immediate posttransplant period because all grafts functioned well. Two important metabolic fates of arginine in the liver are in the detoxification of ammonia by means of the urea cycle, and in the synthesis of nitric oxide (NO). Low extracellular arginine may reflect influx of the amino acid into hepatocytes, resulting in formation of NO in the presence of inducible NO synthase or conversion to ornithine in the presence of arginase in the urea cycle. As the organ stabilizes, restriction of arginine uptake may give rise to the observed increase in extracellular arginine.

Adult↗
PubMed2005

CXC chemokine ligand 16 promotes integrin-mediated adhesion of liver-infiltrating lymphocytes to cholangiocytes and hepatocytes within the inflamed human liver.

Lymphocyte recruitment to the liver is critical for viral clearance in acute hepatitis and in the pathogenesis of chronic inflammatory liver disease when persistent chronic inflammation leads to fibrosis and cirrhosis. Chemokines regulate leukocyte recruitment and positioning in tissues and are thus critical regulators of chronic inflammation. The chemokine CXCL16, which is found in liver tissue, exists in a transmembrane as well as soluble form, providing a potential mechanism for localization to particular structures. We studied the role of CXCL16 and its receptor CXCR6 in lymphocyte recruitment and retention in the liver. A higher proportion of CXCR6(+) T cells was detected in blood of hepatitis C virus patients compared with healthy subjects, and in chronic inflammatory liver disease >60% of intrahepatic T cells expressed CXCR6, including CD4, CD8, and CD56(+) T cells compared with <30% in matched blood samples. CXCR6(+) lymphocytes were found in association with CXCL16(+) bile ducts in portal tracts and with hepatocytes at sites of interface hepatitis. Analysis of CXCL16 expression and subcellular distribution in cultured human cholangiocytes, sinusoidal endothelial cells, and hepatocytes revealed that all three cell types expressed CXCL16, with the strongest staining seen on cholangiocytes. CXCL16 on the cholangiocyte membrane was able to support lymphocyte adhesion by triggering conformational activation of beta(1) integrins and binding to VCAM-1. Thus, CXCL16 can promote lymphocyte adhesion to epithelial cells and may function to attract and retain effector cells that promote biliary and hepatocyte destruction in inflammatory liver disease.

Cell Adhesion↗
PubMed2005

3,4-Methylenedioxymethamphetamine increases neuropeptide messenger RNA expression in rat striatum.

The amphetamine analog 3,4-methylenedioxymethamphetamine (MDMA) is also known as the recreational drug of abuse, Ecstasy. Several neuropeptides are found in striatal neurons postsynaptic to dopamine and serotonin nerve terminals, and changes in neuropeptide neurotransmission may be important for behavioral effects of 3,4-methylenedioxymethamphetamine. This study used in situ hybridization to characterize the effects of 3,4-methylenedioxymethamphetamine on four neuropeptide mRNAs: preprodynorphin, preprotachykinin, neurotensin/neuromedin N, and preproenkephalin. Male, Sprague-Dawley rats received a single administration of 10 mg/kg 3,4-methylenedioxymethamphetamine and were sacrificed 30 min or 3 h later. Three hours after administration, 3,4-methylenedioxymethamphetamine increased preprodynorphin, preprotachykinin, and neurotensin/neuromedin N mRNAs. These increases were most prominent in ventral and medial aspects of the rostral-middle striatum, and then became more dorsally restricted in the caudal striatum. At the 30-minute time point, MDMA significantly decreased the signal for preproenkephalin mRNA in a general manner but did not affect the signal for the other neuropeptide precursors. These data suggest that 3,4-methylenedioxymethamphetamine has a generalized, transient, inhibitory effect on striatopallidal neuron gene expression, and then preferentially influences striatonigral neuropeptide systems at the later time point in a regionally selective manner.

3,4-Methylenedioxyamphetamine↗