(+)-Niguldipine binds with very high affinity to Ca2+ channels and to a subtype of alpha 1-adrenoceptors

Eur J Pharmacol. 1989 May 11;172(2):131-45. doi: 10.1016/0922-4106(89)90004-7.


The enantiomers of the 1,4-dihydropyridine (DHP) niguldipine (3-methyl-5-[3-(4,4-diphenyl-1-piperidinyl)-propyl]- 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-pyridine-3,5-dicarboxylate- hydrochloride) were investigated with respect to their interaction with 1,4-DHP receptors on L-type Ca2+ channels and alpha-adrenoceptors. The Ki values for niguldipine were dependent on the membrane protein concentrations in the radioligand binding assay. 'True' Ki values (at extrapolated 'zero' membrane protein) were determined with guinea-pig membranes for (+)-niguldipine and were found to be 85 pmol/l for the 1,4-DHP receptor of skeletal muscle, 140 pmol/l for that of brain and 45 pmol/l for that of heart. (-)-Niguldipine was approximately 40 times less potent. (+)-Niguldipine (Ki: 78 nmol/l) and (-)-niguldipine (Ki: 58 nmol/l) bound with approximately equal affinity to the alpha 1-adrenoceptors ('alpha 1B') in liver cell membranes. The (+)-niguldipine alpha 1-adrenoceptor inhibition data for rat brain cortex membranes were better fitted by a two-site model. The high-affinity component ('alpha 1A') had a Ki value of 52 pmol/l in competition experiments with [3H]prazosin. The low-affinity site (alpha 1B) had 200- to 600-fold less affinity. (-)-Niguldipine was greater than 40-fold less potent at alpha 1A- but was nearly equipotent to the (+)enantiomer at alpha 1B-sites. (+)-Niguldipine was the most selective compound for discriminating alpha 1A- from alpha 1B-adrenoceptors and is a novel prototype for 1,4-DHPs which bind with nearly equal affinity to skeletal muscle and brain or heart 1,4-DHP receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Channel Blockers / metabolism*
  • Calcium Channels / metabolism*
  • Cerebral Cortex / metabolism
  • Dihydropyridines / metabolism*
  • Guinea Pigs
  • In Vitro Techniques
  • Iodine Radioisotopes
  • Isradipine
  • Liver / metabolism
  • Male
  • Muscles / metabolism
  • Myocardium / metabolism
  • Pyridines / metabolism
  • Rats
  • Receptors, Adrenergic, alpha / metabolism*
  • Stereoisomerism


  • Calcium Channel Blockers
  • Calcium Channels
  • Dihydropyridines
  • Iodine Radioisotopes
  • Pyridines
  • Receptors, Adrenergic, alpha
  • Isradipine
  • niguldipine