<b>Comparison of the Effect of the ATP-Sensitive Potassium Channel Opener YM934 With That of Nitroglycerin on Impaired Coronary Circulation in Dogs</b>

Q4 · MEDICINE

Article

Author: Yamaguchi, Iwao ; Uchida, Wataru ; Masuda, Noriyuki ; Ohtsuka, Sadanori ; Ishikawa, Kimito ; Suzuki, Shoji

We compared the effect of an ATP-sensitive potassium channel opener, YM934, with that of nitroglycerin (NTG) on impaired coronary circulation in dogs. Coronary stenosis was produced in 7 dogs by placing a hydraulic occluder around the proximal left circumflex coronary (LCx) artery and abolishing reactive hyperemia to compromise the LCx flow. The following parameters were measured: the aortic pressure, LCx flow velocity, LCx vessel diameter, LCx peripheral pressure, and segment length in the LCx area. Subsequently, we occluded the LCx artery for 15 seconds and measured the recovery-interval (time required for the segment shortening to return to the preocclusion value). The measurements were recorded under three study conditions: (1) at baseline without LCx stenosis; (2) with LCx stenosis under NTG infusion (3 microg/Kg/min); and (3) with LCx stenosis after intravenous administration of YM934 (0.3 microg/kg). The heart rate and aortic pressure were similar under the three study conditions. Mean LCx flow velocity and segment shortening did not significantly change either. However, LCx peripheral pressure decreased after the induction of stenosis (P < 0.05) and showed no response to either NTG or YM934. YM934 administration significantly increased LCx flow in the presence of LCx stenosis, (P < 0.05), whereas NTG infusion did not. YM934 significantly shortened the recovery-interval of the segment shortening after 15-sec LCx occlusion (P < 0.05), whereas NTG did not. These findings suggest that YM934 improves coronary blood flow and prevents myocardial ischemic damage in severely impaired coronary circulation.

01 Jan 2003·Neurourology and UrodynamicsQ3 · MEDICINE

Effects of ATP‐sensitive K⁺ channel openers and tolterodine on involuntary bladder contractions in a pig model of partial bladder outlet obstruction

Q3 · MEDICINE

Article

Author: Strake, James G. ; Coghlan, Michael J. ; King, Linda L. ; Gopalakrishnan, Murali ; Sullivan, James P. ; Brioni, Jorge D. ; Brune, Michael E. ; Fey, Thomas A.

AbstractAimsTo compare in vivo the efficacy, potency, and bladder–vascular selectivity of ATP‐sensitive potassium channel openers (KCOs), YM934 and (‐)‐cromakalim to a muscarinic antagonist, tolterodine in a novel partial outlet obstructed pig model.MethodsPartially obstructed female Landrace pigs were implanted with telemetry transmitters to allow the continuous measurement of intravesical, abdominal and arterial pressures. A subcutaneous port catheter was used to adjust bladder volume. Bladder and arterial pressure were simultaneously monitored under isoflurane anesthesia before and after increasing i.v. doses of test compounds.ResultsUnder anesthesia, voiding was completely inhibited, but spontaneous, nonvoiding bladder contractions were observed with mean amplitude of 16 ± 1 cm H2O, duration of 35 ± 2 seconds, and intercontraction interval of 43 ± 4 seconds (n = 25). YM934 and (‐)‐cromakalim both caused dose‐dependent decreases in bladder contraction area under the curve (AUC) with effective doses to inhibit AUC by 35% of 3.6 and 14.9 nmol/kg, i.v., respectively. However, concomitant reductions in mean arterial pressure of 12 and 13% were also observed. Tolterodine did not inhibit spontaneous bladder contractions at doses up to 100 nmol/kg, i.v. corresponding to plasma concentrations up to 41 ng/mL.ConclusionsThe superior efficacy of KCOs to inhibit spontaneous bladder contractions relative to tolterodine support the hypothesis that KCOs may provide an alternate therapeutic mechanism to treat symptoms of overactive bladder if bladder‐vascular selectivity can be sufficiently improved. The minimally invasive model described herein appears useful in the preclinical evaluation of potential therapeutics targeted to treat the overactive bladder. Neurourol. Urodynam. 22:147–155, 2003. © 2003 Wiley‐Liss, Inc.

01 Nov 1999·The Journal of pharmacology and experimental therapeutics

Role of an ATP-sensitive potassium channel opener, YM934, in mitochondrial energy production in ischemic/reperfused heart.

Article

Author: Konishi, F ; Taguchi, T ; Takeo, S ; Koshimizu, M ; Ando, T ; Tanonaka, K ; Yogo, T ; Morinaka, T

We examined a possible mechanism of action of an ATP-sensitive potassium (K(ATP)) channel opener, YM934, for the improvement of energy metabolism in hearts subjected to 35-min ischemia and 60-min reperfusion. The treatment with 30 nM YM934 for the final 15 min of preischemia enhanced postischemic recovery of left ventricular developed pressure, attenuated the postischemic rise in left ventricular end-diastolic pressure, and suppressed the release of creatine kinase and ATP metabolites during reperfusion. The treatment also restored myocardial ATP and creatine phosphate contents and attenuated the decrease in mitochondrial oxygen consumption rate during reperfusion. The higher mitochondrial function was also seen in YM934-treated hearts at the end of ischemia. In another set of experiments, myocardial skinned bundles were incubated for 30 min under hypoxic conditions in the presence and absence of YM934, and then mitochondrial oxygen consumption rate was determined. Hypoxia decreased the mitochondrial oxygen consumption rate of skinned bundles to approximately 40% of the prehypoxic value. In contrast, the treatment of skinned bundles with 30 nM YM934 preserved the mitochondrial oxygen consumption rate during hypoxia. The effect of YM934 on the hypoxic skinned bundles was abolished by combined treatment with either the K(ATP) channel blocker glyburide or the mitochondrial K(ATP) channel blocker 5-hydroxydecanoate in a concentration-dependent manner. The results suggest that YM934 is capable of attenuating ischemia/reperfusion injury of isolated perfused hearts due to preservation of mitochondrial function during ischemia, probably through opening of mitochondrial K(ATP) channels.

100 Deals associated with YM-934

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Urinary Incontinence	Phase 2	JP	Yamanouchi Pharmaceutical Co. Ltd. /Over-the-Counter Phar Bus	-
Hypertension	Discovery	JP	Yamanouchi Pharmaceutical Co. Ltd. /Over-the-Counter Phar Bus	-
Urinary Incontinence	Discovery	-	Astellas Pharma, Inc.	-

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis


No Data

YM-934

Overview

Basic Info

Structure

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation