Recent patents on calcium channel blockers: emphasis on CNS diseases.

INTRODUCTION

Altered homeostasis of cell calcium movement is a central stage in multiple diseases of CNS. This explains the great therapeutic interest in blockers for the various subtypes of voltage-activated calcium channels (VACCs) expressed in neurons. Mitigation of Ca(2+) entry excess elicited by those blockers may restore the altered synaptic transmission, synaptic plasticity and gene expression to normal parameters, ending the enhanced neuronal vulnerability.

AREAS COVERED: This review summarize 23 patents on ligands for L-, N- or T-type channels, claimed to have potential therapeutic interest in epilepsy, pain, migraine and neurodegenerative diseases.

EXPERT OPINION: Collections of compounds are generally screened in cell lines expressing a given subtype of VACCs. IC50 to block such channels are often, but not always, provided. In few instances, compounds exhibiting the highest potency in in vitro experiments are also tested in animal models of pain, behavior, epilepsy or Alzheimer's disease. Attempts to develop selectivity for a given VACC subtype with non-peptidic organic ligands have so far failed. Due to their wide tissue expression, such selectivity is crucial for minimizing possible side effects. However, the few data reported by patents does not allow prediction of selectivity of the new compounds in many cases.