Design and biological evaluation of non-peptide analogues of omega-conotoxin MVIIA.
Omega-conotoxin MVIIA, a highly potent antagonist of the N-type voltage sensitive calcium channel, has shown utility in several models of pain and ischemia. We report a series of three alkylphenyl ether based analogues which mimic three key amino acids of the toxin. Two of the compounds have been found to exhibit IC50 values of 2.7 and 3.3 microM at the human N-type voltage sensitive calcium channel.
Menzler
S
S
Parke-Davis Neuroscience Research Centre, Cambridge, UK.
Bikker
J A
JA
Suman-Chauhan
N
N
Horwell
D C
DC
D000818:Animals; D002121:Calcium Channel Blockers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D004341:Drug Evaluation; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D008978:Mollusk Venoms / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D009130:Muscle, Smooth / Q000737:chemistry / Q000166:cytology; D010647:Phenyl Ethers / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012908:Snails / Q000737:chemistry; D013329:Structure-Activity Relationship; D020960:omega-Conotoxins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D008978:Mollusk Venoms; D010647:Phenyl Ethers; D020960:omega-Conotoxins; C078452:ziconotide