Disease relevance of Sch 33844

• In conclusion, a significant regression of left ventricular hypertrophy was obtained after 1 year of treatment with spirapril and isradipine, whereas a similar reduction in medial thickness relative to lumen diameter of subcutaneous small arteries could not be observed in all patients [1].
• Spirapril. A preliminary review of its pharmacology and therapeutic efficacy in the treatment of hypertension [2].
• RESULTS: The pressure-diameter curve of the placebo group was shifted to the left compared to the curves of the control and spirapril groups, showing that renovascular hypertension was associated with isobaric reduction of aortic diameter [3].
• Treatment with spirapril (2-2.5 mg.kg-1.d-1) or zofenopril (12-15 mg.kg-1.d-1) added to the drinking water was started immediately after myocardial infarction or sham operation and continued for six weeks [4].
• Systemic, pulmonary, brachial, renal and hepato-splanchnic hemodynamic effects of spirapril in severe congestive heart failure [5].

Psychiatry related information on Sch 33844

• Second, Spirapril, an inhibitor of the angiotensin-converting enzyme (ACE), which passes the blood-brain barrier, did not influence the alcohol consumption in the TGR(ASrAOGEN)680, but it significantly reduced alcohol intake in wild-type rats [6].

High impact information on Sch 33844

• In dose-finding studies of patients with mild to severe hypertension, spirapril > or = 6 mg once daily produced reductions in blood pressure of approximately 10 to 18 mm Hg (systolic) and 7 to 13 mm Hg (diastolic) [24-hour postdose trough readings at the end of the treatment period] [2].
• One day after renal surgery, dogs were randomly assigned to two groups receiving for two months either the new angiotensin converting enzyme inhibitor spirapril (n = 8) or a placebo capsule (n = 7) [3].
• Heart rate was significantly higher in infarcted animals treated with spirapril and zofenopril than in untreated infarcted animals [4].
• Converting enzyme inhibition after experimental myocardial infarction in rats: comparative study between spirapril and zofenopril [4].
• Peak oxygen consumption tended only to increase in the captopril-treated patients compared with the spirapril-treated patients [7].

Chemical compound and disease context of Sch 33844

• Effects of spirapril and captopril on regional blood flow in chronic congestive heart failure: a comparison between a short- and a long-acting angiotensin-converting enzyme inhibitor [8].

Biological context of Sch 33844

• With the lower dose of spirapril responses of 24-h ambulatory blood pressure to the first dose and to 2 weeks of administration were almost superimposable, although blood pressures in the second half of the dosing interval tended to be higher during chronic treatment [9].
• These compounds were evaluated in vivo for inhibition of angiotensin converting enzyme (ACE), and selected compounds were evaluated for in vitro ACE inhibition (spirapril ID50 16 micrograms/kg; spiraprilat IC50 0.8 nM, ID50 8 micrograms/kg) [10].
• Digoxin pharmacokinetics and spirapril, a new ace inhibitor [11].
• The authors conclude that the ACE inhibitor, Spirapril, when used as an effective antihypertensive agent, preserves renal function, lowers renal vascular resistance, and decreases urinary albumin excretion [12].
• Unlike some other cardiovascular drugs, spirapril does not alter steady-state digoxin kinetics in healthy adults [11].

Anatomical context of Sch 33844

• 2. In SHR, at the established hypertensive stage, the prolonged antihypertensive effect induced by a single oral dose of spirapril was closely correlated to the long-lasting inhibition of ACE in aortae and mesenteric arteries [13].
• Angiotensin-converting enzyme inhibition with spirapril in patients with coronary artery disease [14].
• Spirapril caused a dose-dependent inhibition of the neointimal thickening of the rat carotid artery [15].

Associations of Sch 33844 with other chemical compounds

• Atenolol, isradipine SRO, and spirapril decreased significantly (P < .01) the mean 24-h systolic blood pressure, whereas HCTZ did not [16].
• Results for external quality control samples were in good agreement with the expected values of 0-250 micrograms/L (spirapril, r = 0.997) and 0-300 micrograms/L (spiraprilate, r = 0.999) [17].
• If, after 8 weeks, blood pressure was still not normalized, either the angiotensin-converting enzyme (ACE) inhibitor spirapril at 3 mg (n = 58) or the beta-blocker pindolol at 5 mg (n = 54) was added to the treatment [18].
• In conclusion, spirapril had no effect on lipid metabolism whereas atenolol had some untoward effects [19].
• In terms of blood pressure reduction, however, there is evidence that spirapril is at least as effective as the reference ACE inhibitor, enalapril [20].

Gene context of Sch 33844

• Ramipril, lisinopril, perindopril and spirapril had no significant effect on TNF synthesis suggesting that the effect was not related specifically to the inhibition of ACE [21].
• PAI-1 did not change during spirapril therapy, but during HCT2 treatment it fell, although not significantly, to 9.36 IU/mL from 15.91 with placebo (NS) [22].
• Spirapril stimulated plasma renin activity and suppressed ACE throughout the entire protocol [12].
• 4. At 28 days, plasma renin activity in the spirapril-treated group was significantly elevated compared with that at 14 days (P < 0.05) [23].
• ACE inhibition in chronic renal failure and in the treatment of diabetic nephropathy: focus on spirapril [20].

Analytical, diagnostic and therapeutic context of Sch 33844

• The stiffness index beta was higher (p < 0.05) in the placebo group [0.605(SD 0.304) mm-1] than in either the control group [0.362(0.126) mm-1] or the spirapril group [0.348(0.083) mm-1], suggesting that renovascular hypertension was associated with aortic stiffening [3].
• In crossover design, each also received spirapril or matching placebo capsules during weeks 1 and 2, or 4 and 5 [11].
• All three treatment modalities decreased significantly LV mass index by an average of 10%, although the combination had the greatest blood pressure-lowering effect and spirapril had the least, as assessed by office resting pressures, ambulatory monitoring, and isometric grip testing [24].
• Possible advantages of spirapril compared to other ACE inhibitors are the dual mechanism of elimination, the lack of need for dose titration and a low incidence of cough [25].
• There was a statistically significant reduction of mortality in the pooled spirapril groups compared with placebo, and a trend for reduction of serious cardiovascular adverse events as well as duration of hospitalization [26].

References