PMID- 1530674
OWN - NLM
STAT- MEDLINE
DCOM- 19921020
LR  - 20141120
IS  - 0004-4172 (Print)
IS  - 0004-4172 (Linking)
VI  - 42
IP  - 5
DP  - 1992 May
TI  - Cardiovascular effects of the new generation calcium antagonist 3-pyridine 
      carboxylic acid 
      5-[(cyclopropylamino)carbonyl]-1,4-dihydro-2,6-dimethyl-4-(2-nitropheny l) octyl 
      ester.
PG  - 621-8
AB  - The cardiovascular effects of 3-pyridine carboxylic acid 
      5-[(cyclopropylamino)carbonyl]-1,4-dihydro-2,6-dimethyl-4-(2-nitro phenyl) oxtyl 
      ester (NP-252, CAS 132031-81-3) were examined in anesthetized closed- or 
      open-chest dogs and Langendorff perfused rabbit hearts, and compared with those 
      of nifedipine (NF) and nicardipine (NC). In anesthetized closed- and open-chest 
      dogs, NP-252 (i.v.) selectively increased vertebral and coronary blood flow with 
      a fall in mean blood pressure (MBP). These effects were nearly equipotent with 
      those of NF and NC, but more durable. A similar effect was obtained by 
      intraduodenal administration of NP-252. Also, NP-252 (i.v.) decreased MBP, total 
      peripheral resistance (TPR), left ventricular pressure and dLVP/dtmax while 
      cardiac output (CO) and stroke volume (SV) increased without apparent changes in 
      heart rate and myocardial contractility index. Decreases in MBP and TPR by NP-252 
      were equipotent with NF and NC, whereas increases in CO and SV were more potent 
      than those of the two drugs. These actions of NP-252 were longer than those of 
      the reference agents. Further, in perfused rabbit hearts, NO-252 increased 
      coronary perfusion flow (CPF), accompanying a slight negative inotropy. Its 
      effect in CPF was equipotent with NF and 2 times less than that of NC, however 
      the duration was much longer than those of the reference drugs. On the other 
      hand, the negative inotropic effect of NP-252 was less than NF, but greater than 
      that of NC. In the preparations controlled by pacing, NP-252 and NF lengthened 
      atrio-His bundle conduction time, without affecting His bundle-ventricular 
      conduction time. Lengthening effect of NP-252 was about 4 times less than that of 
      NF. These results suggest that NP-252 acts more selectively on vascular smooth 
      muscle than cardiac muscle, and has almost equipotent but markedly longer 
      vasodilating actions as compared to NF and NC. It may be expected that NP-252 is 
      a new generation of tissue specific and long acting Ca2+ antagonist.
FAU - Hojo, M
AU  - Hojo M
AD  - Pharmacological Department, Nippon Shoji Kaisha, Ltd., Osaka, Japan.
FAU - Teramoto, N
AU  - Teramoto N
FAU - Hata, H
AU  - Hata H
FAU - Katayama, O
AU  - Katayama O
FAU - Tatsumi, H
AU  - Tatsumi H
FAU - Shibata, S
AU  - Shibata S
LA  - eng
PT  - Journal Article
PL  - Germany
TA  - Arzneimittelforschung
JT  - Arzneimittel-Forschung
JID - 0372660
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Dihydropyridines)
RN  - 0 (Vasodilator Agents)
RN  - 132031-81-3 (NP 252)
RN  - CZ5312222S (Nicardipine)
RN  - I9ZF7L6G2L (Nifedipine)
SB  - IM
MH  - Anesthesia
MH  - Animals
MH  - Calcium Channel Blockers/*pharmacology
MH  - Coronary Circulation/drug effects
MH  - Dihydropyridines/*pharmacology
MH  - Dogs
MH  - Female
MH  - Heart Conduction System/drug effects
MH  - Hemodynamics/*drug effects
MH  - In Vitro Techniques
MH  - Male
MH  - Nicardipine/pharmacology
MH  - Nifedipine/pharmacology
MH  - Rabbits
MH  - Vasodilator Agents/pharmacology
EDAT- 1992/05/01 00:00
MHDA- 1992/05/01 00:01
CRDT- 1992/05/01 00:00
PHST- 1992/05/01 00:00 [pubmed]
PHST- 1992/05/01 00:01 [medline]
PHST- 1992/05/01 00:00 [entrez]
PST - ppublish
SO  - Arzneimittelforschung. 1992 May;42(5):621-8.