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April 1, 1985British Journal of PharmacologyOpen Access

Relationship between the stereoselective negative inotropic effects of verapamil enantiomers and their binding to putative calcium channels in human heart

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Key result

Both (-)-verapamil and (+)-verapamil caused cardiodepression and inverted the positive force-frequency staircase in human ventricular tissue while allosterically inhibiting calcium channel binding.

Population

Ventricular preparations and membrane particles from patients with mitral disease and hypertrophic…

Design

Preclinical

Authors

DFD. FerryEli Lilly (United States)HGHartmut GlossmannJohannes Kepler University of LinzAKAlberto J. KaumannElectrophysiology

Discussion

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Implication

Ex vivo human tissue effects warrant no change in verapamil use; leaves open enantiomer-specific actions in patients.

Structured PICO

P
Population
Ventricular preparations and membrane particles from patients with mitral disease and hypertrophic obstructive cardiomyopathy (HOCM), including subendocardial strips from 5 patients with HOCM.
I
Intervention
(-)-verapamil and (+)-verapamil
O
Outcome
Cardiodepression (negative inotropic effect) and inhibition of [3H]-nimodipine binding to calcium channelssurrogate

The similar potency ratios for binding and cardiodepression suggest a common locus of action for verapamil enantiomers within the calcium channel.

Limitations

  • Limited human tissue available per patient restricted the number of assay points
  • In vitro study design may not fully reflect in vivo conditions

Cite This Study

Ferry et al. (1985) studied Mitral valve disease and hypertrophic obstructive cardiomyopathy (n=12). Verapamil enantiomers ((-)-verapamil and (+)-verapamil) vs. Baseline (no verapamil) was evaluated on Cardiodepression and [3H]-nimodipine binding inhibition. Both (-)-verapamil and (+)-verapamil caused cardiodepression and inverted the positive force-frequency staircase in human ventricular tissue while allosterically inhibiting calcium channel binding.

synapsesocial.com/papers/6a08db7e73760a4edcd6048ehttps://doi.org/10.1111/j.1476-5381.1985.tb17375.x
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Also Consider

Synapse has enriched 4 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Convenient apparatus for recording contractions of isolated heart muscle1965 · 138 citations
  2. 2Verapamil therapy: a new approach to the pharmacologic treatment of hypertrophic cardiomyopathy. I. Hemodynamic effects.1979 · 232 citations
  3. 3PROTEIN MEASUREMENT WITH THE FOLIN PHENOL REAGENT1951 · 318,728 citations
  4. 4Target size analysis and molecular properties of Ca2+ channels labelled with [3H]verapamil1984 · 61 citations