scholarly journals Effects of NK1 receptors on gastric motor functions and satiation in healthy humans: results from a controlled trial with the NK1 antagonist aprepitant

2017 ◽  
Vol 313 (5) ◽  
pp. G505-G510 ◽  
Author(s):  
Deepti Jacob ◽  
Irene Busciglio ◽  
Duane Burton ◽  
Houssam Halawi ◽  
Ibironke Oduyebo ◽  
...  
Keyword(s):  
Single Photon ◽  
Controlled Trial ◽  
Photon Emission ◽  
Gastrointestinal Transit ◽  
Gastric Volume ◽  
Emission Computed Tomography ◽  
Nk1 Receptor ◽  
Double Blind ◽  
Nk1 Receptors ◽  
Healthy Humans

Aprepitant, an NK1 receptor antagonist, is approved for the treatment of chemotherapy-induced or postoperative emesis by blocking NK1 receptors in the brain stem vomiting center. The effects of NK1 receptors on gastric functions and postprandial symptoms in humans are unclear; a single, crossover study did not show a significant effect of aprepitant on gastrointestinal transit. Our aim was to compare, in a randomized, double-blind, placebo-controlled, parallel-group study (12 healthy volunteers per group), the effects of aprepitant vs. placebo on gastric emptying of solids (by scintigraphy) with a 320-kcal meal, gastric volumes (GVs; fasting and accommodation by single photon emission-computed tomography ), satiation [maximum tolerated volume (MTV)], and symptoms after a dyspeptogenic meal of Ensure. Aprepitant (125 mg on day 1, followed by 80 mg on days 2–5) or placebo, one tablet daily, was administered for 5 consecutive days. Statistical analysis was by unpaired rank sum test, adjusted for sex difference and body mass index. To assess treatment effects on symptoms, we incorporated MTV in the model. Aprepitant increased fasting, postprandial, and accommodation GV and tended to increase volume to fullness and MTV by ~200 kcal. However, aprepitant increased aggregate symptoms, nausea, and pain scores after ingestion the MTV of Ensure. There was no significant effect of aprepitant on gastric half-emptying time of solids. We conclude that NK1 receptors are involved in the control of GV and in determining postprandial satiation and symptoms. Further studies of the pharmacodynamics and therapeutic role of NK1 receptor antagonists in patients with gastroparesis and dyspepsia are warranted. NEW & NOTEWORTHY Aprepitant increases fasting, postprandial, and accommodation gastric volumes. Aprepitant increases volume to fullness and maximum tolerated volume during a nutrient drink test. NK1 receptors are involved in the control of gastric volume and in determining postprandial satiation and symptoms.

scholarly journals The Effect of Escitalopram on Central Serotonergic and Dopaminergic Systems in Patients with Cervical Dystonia, and Its Relationship with Clinical Treatment Effects: A Double-Blind Placebo-Controlled Trial

Biomolecules ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 880
Author(s):  
Evelien Zoons ◽  
Marina A.J. Tijssen ◽  
Yasmine E.M. Dreissen ◽  
Marenka Smit ◽  
Jan Booij
Keyword(s):  
Cervical Dystonia ◽  
Psychiatric Symptoms ◽  
Single Photon ◽  
Controlled Trial ◽  
Photon Emission ◽  
Placebo Treatment ◽  
Binding Potential ◽  
Emission Computed Tomography ◽  
Double Blind ◽  
Before And After

Purpose: The pathophysiology of cervical dystonia (CD) is thought to be related to changes in dopamine and serotonin levels in the brain. We performed a double-blind trial with escitalopram (selective serotonin reuptake inhibitor; SSRI) in patients with CD. Here, we report on changes in dopamine D2/3 receptor (D2/3R), dopamine transporter (DAT) and serotonin transporter (SERT) binding potential (BPND) after a six-week treatment course with escitalopram or placebo. Methods: CD patients had [123I]FP-CIT SPECT (I-123 fluoropropyl carbomethoxy-3 beta-(4-iodophenyltropane) single-photon emission computed tomography) scans, to quantify extrastriatal SERT and striatal DAT, and [123I]IBZM SPECT (I-123 iodobenzamide SPECT) scans to quantify striatal D2/3R BPND before and after six weeks of treatment with either escitalopram or placebo. Treatment effect was evaluated with the Clinical Global Impression scale for dystonia, jerks and psychiatric symptoms, both by physicians and patients. Results: In both patients treated with escitalopram and placebo there were no significant differences after treatment in SERT, DAT or D2/3R BPND. Comparing scans after treatment with escitalopram (n = 8) to placebo (n = 8) showed a trend (p = 0.13) towards lower extrastriatal SERT BPND in the SSRI group (median SERT occupancy of 64.6%). After treatment with escitalopram, patients who reported a positive effect on dystonia or psychiatric symptoms had significantly higher SERT occupancy compared to patients who did not experience an effect. Conclusion: Higher extrastriatal SERT occupancy after treatment with escitalopram is associated with a trend towards a positive subjective effect on dystonia and psychiatric symptoms in CD patients.

scholarly journals DL-3-n-butylphthalide improves cerebral hypoperfusion in patients with large cerebral atherosclerotic stenosis. A single-center, randomized, double-blind, placebo-controlled study.

2020 ◽  
Author(s):  
Dawei Chen ◽  
Yanwei Yin ◽  
Jin Shi ◽  
Fen Yang ◽  
Kehua Wang ◽  
...  
Keyword(s):  
Placebo Group ◽  
Single Photon ◽  
Photon Emission ◽  
Cerebral Hypoperfusion ◽  
Controlled Study ◽  
Emission Computed Tomography ◽  
Single Center ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Atherosclerotic Stenosis

Abstract Background: DL-3-n-butylphthalide (NBP) was demonstrated to increase the cerebral blood flow (CBF) in the animal models, but there are no clinic studies to verify this. We aimed to explore the effect of NBP on improving cerebral hypoperfusion caused by cerebral large-vessel stenosis. Methods: In this single-center, randomized, double-blind, placebo-controlled study, 120 patients with severe carotid atherosclerotic stenosis and cerebral hypoperfusion in the ipsilateral middle cerebral artery (MCA) were included and randomly assigned into NBP or placebo group as 1:1 radio. Patients in NBP or placebo group received 200mg or 20mg of NBP capsules three times daily for four weeks respectively. Single photon emission computed tomography (SPECT) was used to assess regional CBF (rCBF) in four regions of interest (ROIs) corresponding to MCA before and 12 weeks after the treatment. After therapy, the rCBF change for every ROI and the whole CBF change in MCA territory for every patient were classified into amelioration, stabilization and deterioration respectively. Results: 48 NBP patients (6 with bilateral stenosis) and 46 placebo patients (8 with bilateral stenosis) completed the trial. Overall, both groups had 54 stenotic carotid arteries and 216 ROIs for rCBF change analysis. After therapy, the rCBF in ROIs increased in NBP group (83.5%±11.4% vs. 85.8%±12.5%, p=0.000), whereas no change was found in placebo group (86.9%±11.6% vs. 87.8%±11.7%, p=0.331). Besides, there was higher percentages of ROIs with rCBF amelioration and stabilization in NBP group than in placebo group (93.1% vs. 79.2%, p=0.000). Furthermore, ordinal regression analysis showed that compared with placebo, NBP independently made more patients to have whole CBF amelioration in ipsilateral MCA (Wald-χ2=5.247, OR=3.31, p=0.022). Conclusions: NBP might improve the cerebral hypoperfusion in the patients with carotid artery atherosclerotic stenosis. Trial registration: Chinese Clinical Trial Registry, ChiCTR1900028005, registered December 8th 2019- Retrospectively registered ( http://www.chictr.org.cn/index.aspx ).

Development of a test to measure gastric accommodation in humans

1999 ◽  
Vol 277 (6) ◽  
pp. G1217-G1221 ◽  
Author(s):  
Sjoerd D. Kuiken ◽  
Melvin Samsom ◽  
Michael Camilleri ◽  
Brian P. Mullan ◽  
Duane D. Burton ◽  
...  
Keyword(s):  
Single Photon ◽  
Photon Emission ◽  
Gastric Volume ◽  
Emission Computed Tomography ◽  
Gastric Accommodation ◽  
Distal Stomach ◽  
Tomographic Images ◽  
Coefficients Of Variation ◽  
Health And Disease

Postprandial symptoms of bloating, distension, early satiety, and nausea are associated with impaired postprandial gastric accommodation, which is detectable by means of an intragastric, barostatically controlled balloon in the proximal stomach and by ultrasound in the distal stomach. Our aim was to develop a noninvasive method to measure the entire gastric accommodation reflex. In 10 healthy volunteers, we used single photon emission computed tomography (SPECT) to measure fasting and postprandial gastric volumes. This method involved intravenous injection of99mTc pertechnetate and gastric reconstruction of tomographic images with Analyze software. SPECT-Analyze imaging detects the postprandial gastric accommodation reflex in vivo. Mean fasting gastric volume was 182 ± 11 (SE) ml and mean postprandial volume was 690 ± 32 ml ( P < 0.001). Both proximal and distal segments of stomach showed a two- to almost fourfold difference in volumes postprandially. Intraobserver coefficients of variation in estimated fasting and postprandial volumes were 9 and 8%; interobserver variations were 13 and 12%, respectively. SPECT-Analyze noninvasively measures postprandial gastric (total, proximal, and distal) accommodation in humans. This method appears promising to compare the accommodation response in health and disease and to perform mechanistic studies of the accommodation response.

Effect of oral CCK-1 agonist GI181771X on fasting and postprandial gastric functions in healthy volunteers

2004 ◽  
Vol 287 (2) ◽  
pp. G363-G369 ◽  
Author(s):  
Emma Janet Castillo ◽  
Silvia Delgado-Aros ◽  
Michael Camilleri ◽  
Duane Burton ◽  
Debra Stephens ◽  
...  
Keyword(s):  
Gastric Emptying ◽  
Adverse Effects ◽  
Single Photon ◽  
Photon Emission ◽  
Area Under The Curve ◽  
Gastric Volume ◽  
Oral Solution ◽  
Gallbladder Emptying ◽  
Double Blind ◽  
Computed Tomographic

CCK influences satiation and gastric and gallbladder emptying. GI181771X is a novel oral CCK-1 agonist; its effects on gastric emptying of solids, accommodation, and postprandial symptoms are unclear. Effects of four dose levels of the oral CCK-1 agonist GI181771X and placebo on gastric functions and postprandial symptoms were compared in 61 healthy men and women in a randomized, gender-stratified, double-blind, double-dummy placebo-controlled, parallel group study. Effects of 0.1, 0.5, and 1.5 mg of oral solution and a 5.0-mg tablet of GI181771X on gastric emptying of solids by scintigraphy, gastric volume by 99mTc-single photon emission computed tomographic imaging, maximum tolerated volume of Ensure, and postprandial nausea, bloating, fullness, and pain were studied. On each of 3 study days, participants received their randomly assigned treatment. Adverse effects and safety were monitored. There were overall group effects of GI181771X on gastric emptying ( P < 0.01) and fasting and postprandial volumes ( P = 0.036 and 0.015, respectively). The 1.5-mg oral solution of GI181771X significantly delayed gastric emptying of solids ( P < 0.01) and increased fasting ( P = 0.035) gastric volumes without altering postprandial ( P = 0.056) gastric volumes or postprandial symptoms relative to placebo. The effect of the 5.0-mg tablet on gastric emptying of solids did not reach significance ( P = 0.052). Pharmacokinetic profiles showed the highest area under the curve over 4 h for the 1.5-mg solution and a similar area under the curve for the 0.5-mg solution and 5-mg tablet. Adverse effects were predominantly gastrointestinal and occurred in a minority of participants. GI181771X delays gastric emptying of solids and exhibits an acceptable safety profile in healthy participants. CCK-1 receptors can be modulated to increase fasting gastric volume.

Relationship of gastric emptying and volume changes after a solid meal in humans

2005 ◽  
Vol 289 (2) ◽  
pp. G261-G266 ◽  
Author(s):  
Duane D. Burton ◽  
H. Jae Kim ◽  
Michael Camilleri ◽  
Debra A. Stephens ◽  
Brian P. Mullan ◽  
...  
Keyword(s):  
Gastric Emptying ◽  
Volume Change ◽  
Single Photon ◽  
Photon Emission ◽  
Gastric Volume ◽  
Spect Imaging ◽  
Emission Computed Tomography ◽  
Planar Imaging ◽  
Solid Meal ◽  
3 Dimensional

Noninvasive imaging has been developed to measure gastric volumes. The relationship between gastric emptying and volume postprandially is unclear. The aims were to 1) develop a 3-dimensional (3D) single photon emission-computed tomography (SPECT) method to simultaneously measure gastric volume and emptying postprandially, 2) describe the course of gastric volume change during emptying of the meal, and 3) assess a 3D method measuring gastric emptying. In 30 healthy volunteers, we used 111In-planar and 99mTc-SPECT imaging to estimate gastric emptying and volume after a radiolabeled meal. A customized analysis program of SPECT imaging assessed gastric emptying. A Bland-Altman plot assessed the performance of the new SPECT analysis compared with planar analysis. Gastric volume postprandially exceeds the fasting volume plus meal volume. The course of volume change and gastric emptying differ over time. Higher differences in volumes exist relative to fasting plus residual meal volumes at 15 min (median 763 vs. 568 ml, respectively, P < 0.001), 1 h (median 632 vs. 524 ml, P < 0.001), and 2 h (median 518 vs. 428 ml, P < 0.02), in contrast to similar volumes at 3 h (median 320 vs. 314 ml, P = 0.85). Analysis of SPECT imaging accurately measures gastric emptying compared with planar imaging with median differences of 1% (IQR −2.25 to 2.0) at 1 h, 1% (−3.25 to 2.25) at 2 h, and −2.5% (−4 to 0) at 3 h. Gastric volume exceeds meal volume during the first 2 postprandial hours, and simultaneous measurements of gastric volume and emptying can be achieved with a novel 3D SPECT method.

The Effect of Circulating Adenosine on Cerebral Haemodynamics and Headache Generation in Healthy Subjects

Cephalalgia ◽  
2005 ◽  
Vol 25 (5) ◽  
pp. 369-377 ◽  
Author(s):  
S Birk ◽  
KA Petersen ◽  
C Kruuse ◽  
R Guieu ◽  
O Jonassen ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Cerebral Artery ◽  
Single Photon ◽  
Cerebral Arteries ◽  
Superficial Temporal Artery ◽  
Photon Emission ◽  
Temporal Artery ◽  
Emission Computed Tomography ◽  
Double Blind

Adenosine is an endogenous neurotransmitter that is released from the brain during hypoxia and relaxes isolated human cerebral arteries. Many cerebral artery dilators cause migraine attacks. However, the effect of intravenous adenosine on headache and cerebral artery diameter has not previously been investigated in man and reports regarding the effect of intravenous adenosine on cerebral blood flow are conflicting. Twelve healthy participants received adenosine 80, 120 μg kg-1 min-1 and placebo intravenously for 20 min, in a double-blind, three-way, crossover, randomized design. Headache was rated on a verbal scale (0-10). Regional cerebral blood flow (rCBF) with 133Xe inhalation and single-photon emission computed tomography (SPECT) and MCA flow velocity (VMCA) with transcranial Doppler, were measured in direct sequence. Six participants developed headache during 80 μg kg-1 min-1 and six during 120 μg kg-1 min-1 compared with none on placebo ( P = 0.006). The headache was very mild and predominantly described as a pressing sensation. When correcting data for adenosine-induced hyperventilation, no significant changes in rCBF ( P = 0.22) or VMCA ( P = 0.16) were found between treatments. A significant dilation of the superficial temporal artery (STA) was seen ( P < 0.001). These results show that circulating adenosine has no effect on rCBF or VMCA, while it dilates the STA and causes very mild headache.

Sign in / Sign up

Export Citation Format

Share Document