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Sybertz, E.J. et al.

Angiotensin converting enzyme inhibitory activity of SCH 33844 (spirapril) in rats, dogs and monkeys.

SCH 33844 is a new non-sulfhydryl-containing angiotensin converting enzyme (ACE) inhibitor. SCH 33844 diacid inhibited hydrolysis of the synthetic substrate hippuryl-histidyl-leucine by rabbit lung ACE in vitro with an IC50 (concentration inhibiting enzyme by 50%) of 0.81 nM. The ester was 83 times less active. Intravenous administration of SCH 33844 and its diacid inhibited pressor responses to angiotensin I (AI) in anesthetized rats with calculated ID50's of 16 and 8 micrograms/kg, respectively. Oral administration of SCH 33844 (0.03-1 mg/kg) inhibited AI pressor responses in conscious rats with a duration of 24 hr at the highest dose. The diacid was inactive. Intravenous administration of SCH 33844 (100-1000 micrograms/kg) or its diacid (30 micrograms/kg) to anesthetized dogs inhibited AI pressor activity and potentiated the depressor response to bradykinin. SCH 33844 inhibited AI responses in conscious dogs following oral administration of 0.3-3 mg/kg. Oral administration of SCH 33844 (1 mg/kg) to conscious monkeys inhibited AI pressor responses for the 4 hr duration of study. In conclusion, SCH 33844 is a potent, orally effective ACE inhibitor in rats, dogs and monkeys.[1]

References

Angiotensin converting enzyme inhibitory activity of SCH 33844 (spirapril) in rats, dogs and monkeys. Sybertz, E.J., Baum, T., Ahn, H.S., Desiderio, D.M., Pula, K.K., Tedesco, R., Washington, P., Sabin, C., Smith, E., Becker, F. Archives internationales de pharmacodynamie et de thérapie. (1987) [Pubmed]

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