Search results for "Piperidine"

Cannabinoid type 1 receptor modulates intestinal propulsion by an attenuation of intestinal motor responses within the myenteric part of the peristal…

2007

Cannabinoid-1 (CB1) receptor activation affects gastrointestinal propulsion in vivo. It was our aim to further characterize the involved myenteric mechanisms in vivo and in vitro. In CB1(-/-) mice and wild-type littermates we performed in vivo transit experiments by charcoal feeding and in vitro electrophysiological recordings in mouse small intestinal smooth muscle. Ascending neuronal contraction (ANC) following electrical field stimulation was studied in rat ileum in a partitioned organ bath separating the aboral stimulation site from the oral recording site. The knockout animals displayed an accelerated upper gastrointestinal transit compared to control animals. The CB1 receptor antagoni…

Results of an Open Clinical Trial of Brofaromine (CGP 11 305 A), a Competitive, Selective, and Short-Acting Inhibitor of MAO-A in Major Endogenous De…

1987

In an open clinical trial the authors treated 18 hospitalized patients suffering from endogenous depression with brofaromine (CGP 11305A), a competitive, selective, and short-acting inhibitor of type A monoamine oxidase (MAO). Four patients were defined as good responders, as they had a final HAMD score of between 0 and 7 points. Four patients were judged as improved, with final HAMD scores of between 8 and 15 points, while the remaining eight patients failed to respond (final HAMD score greater than or equal to 16 points). The major observations were a beneficial influence on drive in most patients, while paranoid symptoms worsened markedly, rendering the substance contraindicated in psych…

The Endogenous Opioid System Is Not Involved in Modulation of Opioid-Induced Hyperalgesia

2009

Abstract Some recent studies suggested a role of the endogenous opioid system in modulating opioid-induced hyperalgesia (OIH). In order to test this hypothesis, we conducted a prospective randomized, placebo-controlled, 2-way crossover study in healthy human volunteers. We utilized a well-established model of inducing OIH after a brief exposure to the μ-opioid agonist remifentanil using intradermal electrical stimulation. Patients were exposed to a randomized 90-minute infusion of remifentanil or saline placebo during 2 separate occasions. Development of OIH was quantified using changes in the average radius of the area of secondary hyperalgesia generated by electrical pain stimulation. A 2…

Lorcainide. I. Saturable presystemic elimination.

1979

Human cerebral microcirculation and oxygen saturation during propofol-induced reduction of bispectral index †

2011

† This study investigates the effects of propofol-induced changes in bispectral index (BIS) on cerebral microcirculation and oxygenation during craniotomies. † In 2 mm cerebral depth, an increase in propofol dosage resulted in increased oxygen saturation (srvO2 )w ithout reduction of capillary venous blood flow (rvCBF). † Difference in oxygen content (avDO2) and approximated cerebralmetabolicrateofoxygen (aCMRO2) decreased with an increase in propofol dosage in 2 mm cerebral depth. † Alterations in BIS showed no effect on rvCBF, srvO2 ,a nd haemoglobin amount (rvHb) or on avDO2 or aCMRO2 in 8 mm cerebral depth. † These findings suggest that the CBF/CMRO2 ratio is altered by propofol in a re…

Efficacy and tolerability of lasmiditan, an oral 5-HT1F receptor agonist, for the acute treatment of migraine : a phase 2 randomised, placebo-control…

2012

Lasmiditan (COL-144) is a novel, centrally acting, highly selective 5-HT(1F) receptor agonist without vasoconstrictor activity that seemed effective when given as an intravenous infusion in a proof-of-concept migraine study. We aimed to assess the efficacy and safety of oral lasmiditan for the acute treatment of migraine.In this multicentre, double-blind, parallel-group, dose-ranging study in 43 headache centres in five European countries, patients with migraine with and without aura and who were not using prophylaxis were randomly assigned (1:1:1:1:1) to treat one moderate or severe attack at home with 50 mg, 100 mg, 200 mg, or 400 mg lasmiditan, or placebo. Study drug and placebo were sup…

Spinal Endocannabinoids and CB 1 Receptors Mediate C-Fiber–Induced Heterosynaptic Pain Sensitization

2009

Plastic Pain Perception Drugs and endocannabinoids acting on cannabinoid (CB) receptors have potential in the treatment of certain types of pain. In the spinal cord they are believed to suppress nociception, the perception of pain and noxious stimuli. Pernia-Andrade et al. (p. 760 ) now find that endocannabinoids, which are released in spinal cord by noxious stimulation, may promote rather than inhibit nociception by acting on CB1 receptors. Endocannabinoids not only depress transmission at excitatory synapses in the spinal cord, but also block the release of inhibitory neurotransmitters, thereby facilitating nociception.

Ibrutinib as Treatment for Patients With Relapsed/Refractory Follicular Lymphoma : results From the Open-Label, Multicenter, Phase II DAWN Study

2018

Purpose The Bruton's tyrosine kinase inhibitor ibrutinib has demonstrated clinical activity in B-cell malignancies. The DAWN study assessed the efficacy and safety of single-agent ibrutinib in chemoimmunotherapy relapsed/refractory follicular lymphoma (FL) patients. Methods DAWN was an open-label, single-arm, phase II study of ibrutinib in patients with FL with two or more prior lines of therapy. Patients received ibrutinib 560 mg daily until progressive disease/unacceptable toxicity. The primary objective was independent review committee–assessed overall response rate (ORR; complete response plus partial response). Exploratory analyses of T-cell subsets in peripheral blood (baseline/cycle …

Lorcainide; II. Plasma concentration-effect relationship

1979

Time Course of 5-HT2A Receptor Occupancy in the Human Brain after a Single Oral Dose of the Putative Antipsychotic Drug MDL 100,907 Measured by Posit…

1997

MDL 100,907 is a potent and selective antagonist of 5-HT2A serotonin receptors. Animals studies suggest that MDL 100,907 may behave as an atypical antipsychotic drug. Positron emission tomograph (PET) using [11C]NMSP as the radiotracer was used to define the time course of 5-HT2 receptor occupancy in the human frontal cerebral cortex after a single oral dose of MDL 100,907 (10 or 20 mg) in nine healthy subjects. After the baseline scan each subject was studied three times post dosing at various time points. 5-HT2 occupancies were in the range of 70 and 90% after each dose. While the occupancy remains in this range over 24 hours after 20 mg MDL 100,907, it decreases by about 20% at 24 hours …