Dotarizine versus flunarizine as calcium antagonists in chromaffin cells

  title={Dotarizine versus flunarizine as calcium antagonists in chromaffin cells},
  author={M{\'e}rcedes Villarroya and Luis Gand{\'i}a and Baldomero Lara and Almudena Albillos and Manuela G. L{\'o}pez and Antonio G. Garc{\'i}a},
  journal={British Journal of Pharmacology},
1 Dotarizine is a novel piperazine derivative structurally related to flunarizine that is currently being evaluated in clinical trials for its antimigraine and antivertigo effects. This clinical profile may be related to its Ca2+ antagonist properties. Therefore, the actions of both compounds as calcium antagonists were compared in bovine chromaffin cells. 2 Dotarizine and flunarizine blocked 45Ca2+ uptake into K+ depolarized chromaffin cells (70 mm K+/0.5 mm Ca2+ for 60 s) in a concentration… 
Novel antimigraineur dotarizine releases Ca2+ from caffeine‐sensitive Ca2+ stores of chromaffin cells
Data show that dotarizine shares with thapsigargin and CPA the ability to deplete Ca2+ in the ER; this novel action of dotarIZine could be relevant to its prophylactic effects in migraine.
Differential effects of the neuroprotectant lubeluzole on bovine and mouse chromaffin cell calcium channel subtypes
The results are compatible with the idea that lubeluzole preferentially blocks non‐L‐types of voltage‐dependent Ca2+ channels expressed by bovine and mouse chromaffin cells.
Otilonium: a potent blocker of neuronal nicotinic ACh receptors in bovine chromaffin cells
Otilonium is a potent blocker of nicotinic AChR‐mediated responses and blocked various subtypes of neuronal voltage‐dependent Ca2+ channels at a considerably lower potency than previously reported.


Flunarizine. A reappraisal of its pharmacological properties and therapeutic use in neurological disorders.
Flunarizine is useful in the prophylaxis of migraine, an effective treatment for vertigo and a worthwhile alternative as 'add-on' therapy in patients with epilepsy resistant to conventional drugs.
Dihydropyridine BAY-K-8644 activates chromaffin cell calcium channels
The experiments described here strongly suggest that BAY-K-8644 behaves as a Ca2+-channel activator at the chromaffin cell membrane as shown by Schramm et al.5 in smooth muscle cells.
Different sensitivities to dihydropyridines of catecholamine release from cat and ox adrenals.
From these experiments, it seems clear that distinct subtypes of Ca2+ channels might mediate a similar secretory response in ox and cat adrenal chromaffin cells, at least in the present experimental conditions.
History of Calcium Antagonists
All specific Ca++ antagonists interfere with the uptake of labelled Ca++ into the myocardium and prevent myocardial necrotization arising from deleterious intracellular Ca++ overload; they also block excitation-contraction coupling of vascular smooth muscle, and in this manner, lower Ca++-dependent coronary vascular tone and neutralize all types of experimental coronary spasms.
Classification of calcium antagonists.
  • T. Godfraind
  • Biology, Medicine
    The American journal of cardiology
  • 1987
Bovine chromaffin cells possess FTX-sensitive calcium channels.
It is concluded that the cultured bovine chromaffin cells, in addition to N- and L-type Ca2+ channels, possess a P-type component in their whole-cell currents through their Ca2- channels.