PMID- 11902808
OWN - NLM
STAT- MEDLINE
DCOM- 20020905
LR  - 20190710
IS  - 0022-3573 (Print)
IS  - 0022-3573 (Linking)
VI  - 54
IP  - 3
DP  - 2002 Mar
TI  - The long-lasting anti-anginal effects of CP-060S in a rat model of arginine 
      vasopressin-induced myocardial ischaemia.
PG  - 413-8
AB  - The anti-anginal effect of CP-060S, a new cardioprotective agent that prevents 
      myocardial Na+-, Ca2+-overload and has Ca2+-channel blocking activity, was 
      evaluated in a rat model of arginine8-vasopressin (AVP)-induced cardiac 
      ischaemia. Infusion of AVP (0.2 IU kg(-1)) depressed the electrocardiogram (ECG) 
      ST segment, an index of myocardial ischaemia. Vehicle, CP-060S and diltiazem were 
      given orally 1, 2, 4, 8, 12 and 24 h before the administration of AVP. CP-060S, 
      at 3 mg kg(-1) and 10 mg kg(-1), suppressed AVP-induced ST-segment depression for 
      2 h and 12 h, respectively. In contrast, diltiazem, at 10 and 30 mg kg(-1), 
      suppressed AVP-induced ST-segment depression for only 1 h. The persistent 
      suppression of the AVP-induced ST-segment depression by CP-060S correlated with 
      the time course of changes in its plasma concentration. The minimum effective 
      concentration of CP-060S was estimated to be 30 ng mL(-1) (approximately 50 nM), 
      consistent with its vasorelaxant potency in rat isolated aortic strips 
      (concentration producing 50% relaxation of KCl contraction, IC50 = 32.6+/-8.3 
      nM). Intravenously administered CP-060S, at 300 microg kg(-1) and diltiazem at 
      500 microg kg(-1) showed similar haemodynamic changes, whereas CP-060S, at 300 
      microg kg(-1), significantly suppressed AVP-induced ST-segment depression and 
      diltiazem, at 500 microg kg(-1), had no effect on AVP-induced ST-segment 
      depression. In summary, orally administered CP-060S exerted a long-lasting 
      anti-anginal effect proportionate to the time course of changes in its plasma 
      concentration in a rat model of AVP-induced ischaemia.
FAU - Adachi, Yuichiro
AU  - Adachi Y
AD  - Fuji Gotemba Research Laboratories, Chugai Pharmaceutical Co. Ltd, Gotemba-shi, 
      Shizuoka, Japan.
FAU - Suzuki, Yoshiyuki
AU  - Suzuki Y
FAU - Hatanaka, Takahiro
AU  - Hatanaka T
FAU - Fukazawa, Masanori
AU  - Fukazawa M
FAU - Tamura, Kazuhiko
AU  - Tamura K
LA  - eng
PT  - Journal Article
PL  - England
TA  - J Pharm Pharmacol
JT  - The Journal of pharmacy and pharmacology
JID - 0376363
RN  - 0 (CP 060S)
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Thiazoles)
RN  - 0 (Thiazolidines)
RN  - 0 (Vasoconstrictor Agents)
RN  - 113-79-1 (Arginine Vasopressin)
RN  - EE92BBP03H (Diltiazem)
SB  - IM
MH  - Animals
MH  - Arginine Vasopressin/antagonists & inhibitors/*toxicity
MH  - Calcium Channel Blockers/therapeutic use
MH  - Diltiazem/therapeutic use
MH  - Hemodynamics/drug effects
MH  - Male
MH  - Myocardial Ischemia/chemically induced/*drug therapy
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Thiazoles/*therapeutic use
MH  - Thiazolidines
MH  - Vasoconstrictor Agents/antagonists & inhibitors/toxicity
EDAT- 2002/03/21 10:00
MHDA- 2002/09/06 10:01
CRDT- 2002/03/21 10:00
PHST- 2002/03/21 10:00 [pubmed]
PHST- 2002/09/06 10:01 [medline]
PHST- 2002/03/21 10:00 [entrez]
AID - 10.1211/0022357021778484 [doi]
PST - ppublish
SO  - J Pharm Pharmacol. 2002 Mar;54(3):413-8. doi: 10.1211/0022357021778484.