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

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.

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Analgesic efficacy of the cyclooxygenase-inhibiting nitric oxide donor AZD3582 in postoperative dental pain: Comparison with naproxen and rofecoxib in two randomized, double-blind, placebo-controlled studies

Clinical Therapeutics ◽

10.1016/j.clinthera.2006.09.015 ◽

2006 ◽

Vol 28 (9) ◽

pp. 1279-1295 ◽

Cited By ~ 17

Author(s):

C. Michael Hill ◽

Steen Sindet-Pederson ◽

Robin A. Seymour ◽

John E. Hawkesford ◽

Paul Coulthard ◽

...

Keyword(s):

Nitric Oxide ◽

Analgesic Efficacy ◽

Dental Pain ◽

Nitric Oxide Donor ◽

Double Blind ◽

Double Blind Placebo ◽

Postoperative Dental Pain

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

Gut ◽

10.1136/gut.42.3.410 ◽

1998 ◽

Vol 42 (3) ◽

pp. 410-413 ◽

Cited By ~ 17

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.

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

Cephalalgia ◽

10.1046/j.1468-2982.1996.1603169.x ◽

1996 ◽

Vol 16 (3) ◽

pp. 169-174 ◽

Cited By ~ 25

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.

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Faculty Opinions recommendation of Effect of hyperacute administration (within 6 hours) of transdermal glyceryl trinitrate, a nitric oxide donor, on outcome after stroke: subgroup analysis of the efficacy of nitric oxide in stroke (ENOS) trial.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725850686.793510844 ◽

2015 ◽

Author(s):

Andrea Semplicini

Keyword(s):

Nitric Oxide ◽

Glyceryl Trinitrate ◽

Subgroup Analysis ◽

Nitric Oxide Donor

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

Journal of International Medical Research ◽

10.1177/030006059702500106 ◽

1997 ◽

Vol 25 (1) ◽

pp. 41-44 ◽

Cited By ~ 16

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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