Document Detail

Antihypertensive effect of the novel water-soluble calcium antagonist (+/-)-3-(4-allyl-1-piperazinyl)-2,2-dimethylpropyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate dihydrochloride in rats.
MedLine Citation:
PMID:  7818582     Owner:  NLM     Status:  MEDLINE    
The antihypertensive effect of (+/-)-3-(4-allyl-1-piperazinyl)-2,2-dimethylpropyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate dihydrochloride (NKY-722, CAS 117241-46-0) was examined in conscious spontaneously hypertensive rats (SHR), normotensive Wistar rats (NWR) and anesthetized NWR, and its vasodilatory effect was investigated in the perfused NWR mesenteric vascular bed. NKY-722 and nicardipine administered intravenously (10-100 micrograms/kg) and orally (0.3-10 mg/kg) lowered blood pressure dose-dependently with an increase in heart rate in conscious SHR and NWR. The effects of NKY-722 were slower in onset and longer-lasting than those of nicardipine, and were more marked in SHR than in NWR. The effect of NKY-722 was roughly the same as that of nicardipine on intravenous administration. However, NKY-722 was 4-8 times more potent than nicardipine on oral administration. In anesthetized NWR, the hypotensive effects of NKY-722 administered via the femoral vein, portal vein and duodenum were examined in comparison with those of nicardipine. The findings suggest that NKY-722 is more efficiently absorbed from the gastro-intestinal tract and more resistant to the hepatic first pass effect than nicardipine. In the perfused NWR vascular bed, NKY-722 and nicardipine (0.01-1.0 microgram) attenuated the pressor response to KCl dose-dependently. The effect of NKY-722 was slower in onset and longer-lasting than that of nicardipine. In conclusion; NKY-722 has a potent, slow-onset and long-lasting antihypertensive activity, which is mainly attributed to its slow-onset and long-lasting vasodilatory action. NKY-722 is expected to be a useful antihypertensive drug.
K Wada; S Nakamura; S Morishita; M Kanda; H Matsui; F Fukata; H Shirahase
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Arzneimittel-Forschung     Volume:  44     ISSN:  0004-4172     ISO Abbreviation:  Arzneimittelforschung     Publication Date:  1994 Oct 
Date Detail:
Created Date:  1995-02-06     Completed Date:  1995-02-06     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  0372660     Medline TA:  Arzneimittelforschung     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  1112-6     Citation Subset:  IM    
Research Laboratories, Kyoto Pharmaceutical Industries, Ltd., Japan.
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MeSH Terms
Antihypertensive Agents / pharmacokinetics,  pharmacology*
Blood Pressure / drug effects
Calcium Channel Blockers / pharmacokinetics,  pharmacology*
Dihydropyridines / pharmacokinetics,  pharmacology*
Dose-Response Relationship, Drug
Heart Rate / drug effects
Nicardipine / pharmacokinetics,  pharmacology
Potassium Chloride / pharmacology
Rats, Inbred SHR
Rats, Wistar
Splanchnic Circulation / drug effects
Reg. No./Substance:
0/Antihypertensive Agents; 0/Calcium Channel Blockers; 0/Dihydropyridines; 117241-46-0/NKY 722; 55985-32-5/Nicardipine; 7447-40-7/Potassium Chloride

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