scholarly journals Glyceryl trinitrate in first-episode psychosis unmedicated with antipsychotics: A randomised controlled pilot study

2020 ◽  
Vol 34 (8) ◽  
pp. 839-847 ◽  
Author(s):  
Kate Merritt ◽  
Ana Catalan ◽  
Samuel Cowley ◽  
Arsime Demjaha ◽  
Matthew Taylor ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Glyceryl Trinitrate ◽  
Verbal Memory ◽  
Alternative Hypothesis ◽  
Controlled Trial ◽  
Verbal Learning ◽  
Nitric Oxide Donor ◽  
Psychotic Symptoms ◽  
First Episode ◽  
Double Blind

Background: There is a pressing need for new classes of treatment for psychosis. A key therapeutic target for novel compounds is the NMDA receptor, which may be modulated by nitric oxide donors such as sodium nitroprusside (SNP). Recent studies of SNP in patients with psychosis have mixed results, and the drug has to be administered intravenously. Glyceryl trinitrate (GTN) is a well-established cardiovascular medicine that is also a nitric oxide donor, and can be given orally. Aims: We explored the safety and potential effects of GTN in unmedicated patients with a first episode of psychosis. Methods: This was a single-centre, randomised, double-blind, placebo-controlled trial from December 2016 to April 2019 (ClinicalTrials.gov identifier: NCT02906553). Patients received 3 × sprays of GTN or placebo for three consecutive days, and were re-assessed on Days 1, 2, 3 and 7. The primary outcome was cognition (Jumping to Conclusions task), secondary outcomes were symptoms (Positive and Negative Syndrome Scale (PANSS)), verbal memory (Hopkins Verbal Learning task), and mood (Bond–Lader Visual Analogue Scales). Results: Nineteen patients were randomised, and 13 participants were included in the analyses. Compared with placebo, GTN was well tolerated, but was not associated with significant effects on cognition, symptoms, or mood. Bayesian statistics indicate that our results were 2× more likely under the null hypothesis than the alternative hypothesis, providing anecdotal evidence that GTN does not improve psychotic symptoms. Conclusions: We found no indication of an effect of GTN on symptoms of psychosis or cognition.

scholarly journals T40. GLYCERYL TRINITRATE IN FIRST EPISODE PSYCHOSIS UNMEDICATED WITH ANTIPSYCHOTICS: A RANDOMISED CONTROLLED FEASIBILITY STUDY

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S246-S247
Author(s):  
Kate Merritt ◽  
Ana Catalan ◽  
Samuel Cowley ◽  
Arsime Demjaha ◽  
Matthew Taylor ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Clinical Trials ◽  
Controlled Trial ◽  
Verbal Learning ◽  
Nitric Oxide Donor ◽  
Psychotic Symptoms ◽  
First Episode ◽  
Nitric Oxide Donors ◽  
Double Blind ◽  
Randomised Controlled

Abstract Background There is a pressing need for new classes of treatment for psychosis. A key therapeutic target for novel compounds is the NMDA receptor, which may be modulated by nitric oxide donors such as sodium nitroprusside (SNP). Recent early phase studies of SNP in patients with psychosis have had mixed results, and the drug has to be administered intravenously. GTN is a well-established cardiovascular medicine that is also a nitric oxide donor, and can be given orally. We explored the safety and effectiveness of GTN in unmedicated patients with a first episode of psychosis. Methods A single-centre, randomized, double-blind, placebo-controlled trial was conducted from December 2016 to April 2019 (ClinicalTrials.gov identifier: NCT02906553). Patients with a first episode of psychosis were recruited from the South London and Maudsley NHS Trust, London, UK. Nineteen patients were randomised to receive 3 x sprays of GTN or placebo for 3 consecutive days, and re-assessed on Day 7. Thirteen participants were included in the final analyses. At each assessment point, symptom levels were measured using the Positive and Negative Syndrome Scale (PANSS), and cognitive performance was evaluated using the Jumping to Conclusions (JTC) and the Hopkins Verbal Learning (HVLT) tasks. Results Compared to placebo, GTN was well tolerated, but it was not associated with significant effects on either psychotic symptoms or cognition. Bayesian statistics indicated with moderate confidence that GTN does not have a therapeutic effect. Discussion This study indicates that nitric oxide donors are not therapeutically beneficial in psychosis. It also highlights the difficulties in recruiting unmedicated patients with psychosis. Future clinical trials would benefit from frameworks built into clinical services, to signpost patients not responding to medication and those discontinuing medication to clinical trials of alternatives.

Oral nitric-oxide donor glyceryl-trinitrate induces sensitization in spinal cord pain processing in migraineurs: A double-blind, placebo-controlled, cross-over study

2011 ◽  
Vol 15 (5) ◽  
pp. 482-490 ◽  
Author(s):  
Armando Perrottal ◽  
Mariano Serraol ◽  
Cristina Tassorellil ◽  
Natalia Arce-Leall ◽  
Elena Guaschinol ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Spinal Cord ◽  
Glyceryl Trinitrate ◽  
Nitric Oxide Donor ◽  
Pain Processing ◽  
Double Blind ◽  
Double Blind Placebo

Role of nitric oxide signaling in the antidepressant mechanism of action of ketamine: A randomized controlled trial

2021 ◽  
Vol 35 (2) ◽  
pp. 124-127
Author(s):  
Laura Bevilacqua ◽  
Alex Charney ◽  
Charlotte R Pierce ◽  
Samantha M Richards ◽  
Manish K Jha ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Sodium Nitroprusside ◽  
Mechanism Of Action ◽  
Controlled Trial ◽  
Nitric Oxide Donor ◽  
Controlled Study ◽  
Primary Role ◽  
Double Blind ◽  
Nitric Oxide Signaling ◽  
Antidepressant Effects

Ketamine is an N-methyl-D-aspartate receptor antagonist with rapid antidepressant effects. Studies suggest that inhibition of nitric oxide synthesis plays a role in the mechanism of action of ketamine. This randomized, placebo-controlled study investigated whether co-administration of sodium nitroprusside, a nitric oxide donor, compared to placebo, would attenuate the antidepressant and dissociative effects of ketamine. Sixteen ketamine responders were randomized to a double-blind infusion of ketamine co-administered with placebo or sodium nitroprusside. Our findings show no difference between the two conditions suggesting that the nitric oxide pathway may not play a primary role in ketamine’s antidepressant or dissociative effects. The study is registered at clinicaltrials.gov (NCT03102736).

scholarly journals Effect of the nitric oxide donor, glyceryl trinitrate, on human gall bladder motility

Gut ◽  
1998 ◽  
Vol 42 (3) ◽  
pp. 410-413 ◽  
Author(s):  
R Greaves ◽  
J Miller ◽  
L O’Donnell ◽  
A McLean ◽  
M J G Farthing
Keyword(s):  
Nitric Oxide ◽  
Gall Bladder ◽  
Glyceryl Trinitrate ◽  
Bladder Volume ◽  
Nitric Oxide Donor ◽  
Fasting State ◽  
Double Blind ◽  
Bladder Emptying

Background—Nitric oxide is a major neurotransmitter in non-adrenergic, non-cholinergic (NANC) pathways. NANC inhibitory innervation has been shown in human gall bladder muscle in vitro; the role of nitric oxide in human gall bladder emptying however is undefined.Aims—To study the effect of glyceryl trinitrate, a nitric oxide donor, on gall bladder emptying in healthy subjects using a randomised, double blind, crossover, placebo controlled design.Methods—Ultrasonographic gall bladder volume was measured in the fasting state in eight healthy volunteers after randomised administration of either glyceryl trinitrate 1200 μg buccal spray or placebo spray. On two further occasions, after randomised administration of either glyceryl trinitrate 1200 μg buccal spray or placebo spray, gall bladder volumes were also measured after a liquid test meal.Results—Glyceryl trinitrate significantly increased fasting gall bladder volume to a mean of 114% (SEM 5%) of pretreatment volume (p=0.039). Glyceryl trinitrate also significantly impaired gall bladder emptying between five and 40 minutes postprandially. Gall bladder ejection fraction was also reduced after glyceryl trinitrate compared with placebo (43 (6.9)% versus 68.4 (6.5)%, p=0.016).Conclusions—This study shows that glyceryl trinitrate produces gall bladder dilatation in the fasting state and reduces postprandial gall bladder emptying, suggesting that nitric oxide mechanisms may be operative in the human gall bladder in vivo.

Effect of a Nitric Oxide Donor (Glyceryl Trinitrate) on Nociceptive Thresholds in Man

Cephalalgia ◽  
1996 ◽  
Vol 16 (3) ◽  
pp. 169-174 ◽  
Author(s):  
LL Thomsen ◽  
J Brennum ◽  
HK Iverson ◽  
J Olesen
Keyword(s):  
Nitric Oxide ◽  
Glyceryl Trinitrate ◽  
Animal Studies ◽  
Crossover Design ◽  
Nitric Oxide Donor ◽  
Temporal Region ◽  
Double Blind ◽  
No Donor ◽  
Pain Detection ◽  
Nociceptive Input

Several animal studies suggest that nitric oxide (NO) plays a role in central and peripheral modulation of nociception. Glyceryl trinitrate GTN) exerts its physiological actions via donation of NO. The purpose of the present study was to examine the effect of this NO donor on nociceptive thresholds in man. On two different study days separated by at least, week 12 healthy subjects received a staircase infusion of GTN (0.015, 0.25. 1.0, 2.0 mg/kg/min. 20 min each dose) or placebo in a randomized double-blind crossover design. Before the infusion and after 15 min of infusion on each dose, pressure pain detection and tolerance thresholds were determined by pressure a gometry (Somomedic AB, Sweden) in three different anatomic regions (finger, a temporal region with interposed myofascial tissue and a temporal region without interposed myofascial tissue. Relative to placebo, the three higher GTN doses induced a decrease in both detection and tolerance thresholds in the temporal region with interposed myofascial tissue ( p=0.003 detection and p=0.002 tolerance threshold: Friedman). No such changes were observed in the other two stimulated regions. These results could reflect central facilitation of nociception by NO. However, we regard convergence, of nociceptive input from pericranial myofascial tissue and from cephalic blood vessels dilated by NO as a more likely, explanation of our findings.

scholarly journals Paraoxonase 1, B Vitamins Supplementation, and Mild Cognitive Impairment

2021 ◽  
pp. 1-19
Author(s):  
Joanna Perła-Kaján ◽  
Olga Włoczkowska ◽  
Anetta Zioła-Frankowska ◽  
Marcin Frankowski ◽  
A. David Smith ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Controlled Trial ◽  
Verbal Learning ◽  
Cognitive Status ◽  
B Vitamins ◽  
Paraoxonase 1 ◽  
Phenyl Acetate ◽  
Double Blind ◽  
Trail Making

Background: Identification of modifiable risk factors that affect cognitive decline is important for the development of preventive and treatment strategies. Status of paraoxonase 1 (PON1), a high-density lipoprotein-associated enzyme, may play a role in the development of neurological diseases, including Alzheimer’s disease. Objective: We tested a hypothesis that PON1 status predicts cognition in individuals with mild cognitive impairment (MCI). Methods: Individuals with MCI (n = 196, 76.8-years-old, 60% women) participating in a randomized, double-blind placebo-controlled trial (VITACOG) were assigned to receive a daily dose of folic acid (0.8 mg), vitamin B12 (0.5 mg) and B6 (20 mg) (n = 95) or placebo (n = 101) for 2 years. Cognition was analyzed by neuropsychological tests. Brain atrophy was quantified in a subset of participants (n = 168) by MRI. PON1 status, including PON1 Q192R genotype, was determined by quantifying enzymatic activity of PON1 using paraoxon and phenyl acetate as substrates. Results: In the placebo group, baseline phenylacetate hydrolase (PhAcase) activity of PON1 (but not paraoxonase activity or PON1 Q192R genotype) was significantly associated with global cognition (Mini-Mental State Examination, MMSE; Telephone Inventory for Cognitive Status-modified, TICS-m), verbal episodic memory (Hopkins Verbal Learning Test-revised: Total Recall, HVLT-TR; Delayed Recall, HVLT-DR), and attention/processing speed (Trail Making A and Symbol Digits Modalities Test, SDMT) at the end of study. In addition to PhAcase, baseline iron and triglycerides predicted MMSE, baseline fatty acids predicted SDMT, baseline anti-N-Hcy-protein autoantibodies predicted TICS-m, SDMT, Trail Making A, while BDNF V66M genotype predicted HVLT-TR and HVLT-DR scores at the end of study. B-vitamins abrogated associations of PON1 and other variables with cognition. Conclusion: PON1 is a new factor associated with impaired cognition that can be ameliorated by B-vitamins in individuals with MCI.

Effects of L-citrulline supplementation on nitric oxide and antioxidant markers after high-intensity interval exercise in young men: a randomized controlled trial

2021 ◽  
pp. 1-23
Author(s):  
Kosar Valaei ◽  
Javad Mehrabani ◽  
Alexei Wong
Keyword(s):  
Nitric Oxide ◽  
High Intensity ◽  
Controlled Trial ◽  
Young Men ◽  
No Production ◽  
Double Blind ◽  
Interval Exercise ◽  
Damage Indices ◽  
High Intensity Interval ◽  
Antioxidant Markers

Abstract L-citrulline (L-Cit) is a nonessential amino acid that stimulates nitric oxide (NO) production and improves exercise performance by reducing muscle damage indices; however, the direct benefits of L-Cit on antioxidant markers are unclear. The aim of this study was to examine antioxidant responses to high-intensity interval exercise following acute L-Cit supplementation. Nine young men (21 ± 1 years) participated in a double-blind crossover study in which they received 12 g of L-Cit and placebo (PL) an hour prior to high-intensity interval exercise on two occasions, separated by a seven-day washout period. Blood samples were obtained before (PRE), immediately after (IP), 10 (10P), and 30 min after exercise (30P) from the cubital vein using standard procedures. Serum concentrations of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and NO metabolites (NOx) were measured. The exercise protocol significantly elevated SOD (p = 0.01) and GPx (p = 0.048) from PRE to 10P in the L-Cit group with greater changes than the PL group. CAT concentrations increased IP (p = 0.014) and remained elevated at 10P (p = 0.03) and 30P (p = 0.015) in both the L-Cit and PL conditions. NOx concentrations increased IP (p = 0.05) in the L-Cit group with greater changes than PL group in PRE to IP, PRE to 10P, and PRE to 30P (p < 0.05). Our data indicate that L-Cit supplementation (single 12 g dose pre-exercise) induces improvements in antioxidant markers following a session of high-intensity interval exercise in young men.

Transdermal Nitroglycerine in the Management of Pain Associated with Primary Dysmenorrhoea: A Multinational Pilot Study

1997 ◽  
Vol 25 (1) ◽  
pp. 41-44 ◽  
Author(s):  
O Ré ◽  
Keyword(s):  
Nitric Oxide ◽  
Pain Relief ◽  
Muscle Relaxation ◽  
Nitric Oxide Donor ◽  
Controlled Study ◽  
Smooth Muscle Relaxation ◽  
Uterine Contractility ◽  
Double Blind ◽  
Patch Application ◽  
Endogenous Nitric Oxide

Endogenous nitric oxide mediates smooth-muscle relaxation with subsequent vasodilatation in the vascular, pulmonary, gastrointestinal and genitourinary tissues. Transdermal nitroglycerine (a nitric oxide donor) has been found effective in inhibiting uterine contractility during premature labour. Sixty-five women with histories of moderate-to-severe pain associated with menses were treated with nitroglycerine patches that delivered 0.2 or 0.1 mg/h. Patches were applied as necessary during the first 3 days of the menstrual cycle for up to three consecutive cycles. Pain intensity was assessed at baseline and at 30 min and at 1, 2 and 4 h after patch application. Most patients obtained pain relief with the first dose of the first day. Pain relief was satisfactory to excellent in 90% of the patients. Headache was reported by 20% of the patients, most often in patients using two consecutive patches. A randomized, double-blind, placebo-controlled study is underway in an attempt to confirm the above findings.

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