The cardiovascular effects of YM-16151-4 were evaluated in rats and dogs. In conscious rats, YM-16151-4 (3-30 mg/kg p.o.) produced a dose-dependent hypotensive effect without increasing heart rate (HR) and plasma renin activity (PRA). Nifedipine (3-10 mg/kg p.o.) produced a dose-dependent hypotensive effect but significantly increased HR and PRA. Atenolol (30 mg/kg p.o.) decreased PRA but did not decrease blood pressure and HR. The cardiovascular effects of the combination of nifedipine and atenolol were similar to those of YM-16151-4. It is interesting that the time course of the hypotensive effect of YM-16151-4 was similar to that of its beta 1-adrenoceptor blocking effect, although the time courses of these effects of the combination of nifedipine and atenolol were different. In conscious dogs, YM-16151-4 (0.3-10 mg/kg p.o.) also produced a long-lasting hypotensive effect with almost no effect on HR and PQ-interval. The time course of the beta 1-adrenoceptor blocking effect was similar to that of its hypotensive effect. Furthermore, during 10-day repeated oral administration, neither tolerance nor augmentation was observed in the hypotensive and beta 1-adrenoceptor-blocking effects. In conclusion, the present results indicate that YM-16151-4 is an effective and long-lasting hypotensive agent that does not increase HR and PRA. These effects of YM-16151-4 may be attributable to its calcium-entry-blocking and beta 1-adrenoceptor-blocking activities, and the ratio of two activities was constant after single and repeated oral administrations.

01 May 1993·Journal of Cardiovascular PharmacologyQ4 · MEDICINE

Antianginal Effects of YM-16151–4 in Various Experimental Angina Models

Q4 · MEDICINE

Article

Author: Takenaka, Toichi ; Uchida, Wataru ; Shibasaki, Kumiko ; Asano, Masaharu

The antianginal effects of YM-16151-4, a combined calcium entry blocking and beta 1-adrenoceptor blocking agent, were evaluated in various experimental angina models and compared with those of nifedipine and propranolol. In anesthetized dogs, YM-16151-4 (0.3 and 1 mg/kg intravenously, i.v.) increased coronary blood flow and reduced myocardial oxygen consumption (MVO2). In isolated dog coronary arteries, YM-16151-4 concentration-dependently inhibited 3,4-diaminopyridine-induced rhythmic contractions with an IC50 value of 91 nM. In anesthetized rats, YM-16151-4 also inhibited the ST-segment depression induced by vasopressin (0.5 U/kg i.v.) with an ED50 value of 29 mg/kg orally, (p.o.). Nifedipine was also effective in these models, but propranolol was not. In addition, YM-16151-4 (0.3 mg/kg i.v.) inhibited the ST-segment elevation in the epicardial ECG induced by coronary artery occlusion in anesthetized dogs. Propranolol (1 mg/kg i.v.) also inhibited this elevation, but nifedipine (0.003 mg/kg i.v.) did not. In anesthetized dogs, furthermore, the prolongation of PQ-interval induced by YM-16151-4 was almost the same as that induced by propranolol. These results demonstrate that YM-16151-4, in contrast to nifedipine and propranolol, is fully effective in these various types of angina models. Thus, YM-16151-4 is expected to prove a valuable antianginal agent in treatment of various types of angina pectoris, with these antianginal effects resulting from the sum of its calcium entry blocking and beta 1-adrenoceptor blocking activities.

01 Jan 1992·Journal of Cardiovascular PharmacologyQ4 · MEDICINE

Cardiovascular Effects of a Novel Calcium Entry Blocking and Selective prAdrenoceptor Blocking Agent, YM-16151–4, in Anesthetized and Conscious Dogs

Q4 · MEDICINE

Article

Author: Uchida, Wataru ; Shibasaki, Kumiko ; Asano, Masaharu

Cardiovascular effects of YM-16151-4, a combined calcium entry blocking and beta 1-adrenoceptor blocking agent, were evaluated in dogs. In anesthetized dogs, YM-16151-4 (0.01-1 mg/kg intravenously, i.v.) dose-dependently increased coronary blood flow (CBF) and decreased mean blood pressure (MBP), total peripheral resistance (TPR), dP/dtmax, double product, and left ventricular (LV) work without increasing heart rate (HR) and cardiac output (CO). YM-16151-4 increased vertebral blood flow as well as CBF, but had no effect on carotid, mesenteric, renal, and femoral blood flow. Coronary vasodilating activity of YM-16151-4 was also observed after intracoronary artery injection (i.a.). In anesthetized and vagotomized dogs, YM-16151-4 dose-dependently inhibited isoproterenol (0.2 micrograms/kg i.v.)-induced tachycardia and decrease in diastolic BP (DBP), with ED50 values of 0.039 and 0.52 mg/kg i.v., respectively. In conscious dogs, YM-16151-4 (0.1-1 mg/kg i.v.) produced a dose-dependent hypotensive effect with no effect on HR or PQ-interval. The hypotensive effect of YM-16151-4 (0.3 and 1 mg/kg i.v.) reached its maximum approximately 1-2 h after each dosing and lasted 6-8 h. These results suggest that YM-16151-4 actually behaves as a hybrid compound, combining calcium entry blocking and beta 1-adrenoceptor blocking activities, and that this compound could be a novel long-acting antianginal and antihypertensive agent.

100 Deals associated with YM-161511

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Angina Pectoris	Phase 1	EU	-	-
Angina Pectoris	Phase 1	US	-	-
Angina Pectoris	Phase 1	US	-	-
Angina Pectoris	Phase 1	-	Astellas Pharma, Inc.	-
Angina Pectoris	Phase 1	JP	Yamanouchi Pharmaceutical Co. Ltd. /Over-the-Counter Phar Bus	-
Angina Pectoris	Phase 1	EU	-	-
Angina Pectoris	Phase 1	-	Astellas Pharma, Inc.	-
Angina Pectoris	Phase 1	JP	Yamanouchi Pharmaceutical Co. Ltd. /Over-the-Counter Phar Bus	-
Hypertension	Phase 1	EU	-	-
Hypertension	Phase 1	EU	-	-

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-161511

Overview

Basic Info

Structure/Sequence

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation