Wenckeback (1914) reported on effects of quinine alkaloids in certain arrhythmias which impressed Frey (1918) who studied use of cinchonine, quinine & quinidine in AF & found quinidine the most effective;
Mautz (1936) demonstrated application of procaine incr. ventricular muscle threshold to electrical stimulation & this was later demonstrated to be similar action to quinidine;
procainamide discovered in 1951 after a search of congeners of procaine which was rapidly hydrolysed & had CNS effects;
Procainamide however tended to produce a SLE-like syndrome thus prompted search for other drugs with quinidine-like activity:
Disopyramide introduced in 1978 but had significant antimuscarinic & -ve inotropy;
Moricizine developed in USSR in 1960's is a recent candidate;
lignocaine used as a LA was introduced as antiarrhythmic in 1962 for emergency Rx of VT/VF after cardiac Sx or AMI;
2 orally effective relatives of lignocaine became available:
tocainide in 1984;
mexiletine in 1986;
phenytoin has been used since 1938 for seizures, & was found to be effective in VT in expt. AMI in dogs in 1950, & has since been used in man esp. for VT/VF assoc. with digoxin & tricyclic toxicity;
flecainide was introduced in 1986 (US), & later encainide was introduced;
Bretylium was approved for resist. VT/VF in 1978 (US);
amiodarone was approved for resistant VT or recurrent VF in 1986 (US);