236 1. lODOACETATE AND lODOACETAMIDE 



cats, Bornschein (1958) noted a temporary increase in the spontaneous ac- 

 tivity, and suggested that iodoacetate may affect primarily the photorecep- 

 tors and that these participate in the spontaneous discharge. Quite possibly 

 the fall in the resting membrane potential of the visual cells (Miiller-Limm- 

 roth and Bliimer, 1957) is responsible for this spontaneous activity, since the 

 lowering of the resting potential within a certain range usually increases 

 excitability and automaticity. The EKG changes resulting from a single 

 intravenous injection of iodoacetate are slowly reversible, the b wave re- 

 covering to more than half-normal within 5-6 hr and to normal within 1 

 day (Noell, 1952). It would be important to know what is involved in this 

 reversibility. The pupillary reflex to light is abolished early, as might be 

 expected, so that Schubert and Bornschein (1951) wondered whether the 

 primary attack is on glycolysis or on the ])hotochemical reactions. Wald 

 and Brown (1951, 1952) found that even high concentrations of iodoacetate 

 (30 mM) do not inhibit the regeneration of rhodopsin, although the mer- 

 curials block this very readily. There is thus no evidence that photochem- 

 ical reactions are directly affected, but the fundamental reactions linking 

 photon absorption with the membrane changes involved in the initiation 

 of impulses have never been studied. Retinal edema is marked after iodo- 

 acetate, being maximal in 30 min, and this may result from interference 

 with the active transport of water (Graymore, 1958). It is not known if the 

 swelling is in any way responsible for obliteration of the retinal blood ves- 

 sels, a mechanism which has been postulated for later degenerative changes, 

 but it seems highly unlikely that it would play a role in the alterations 

 of the ERG. If glycolytic inhibition is responsible for the ERG changes, 

 other inhibitors of the EM pathway might be expected to produce similar 

 effects. Karli (1952) observed no effects of fluoride in rabbits, but it was 

 given by stomach tube and probably did not reach the retina in sufficiently 

 high concentration, whereas Babel and Ziv (1956) found temporary ERG 

 changes from injections of fluoride, although no damage was produced, 

 probably due to the rapid reversal of the inhibition. Other SH agents, such 

 as the mercurials, arsenicals, and o-iodosobenzoate, do not produce these 

 retinal changes, although bromoacetate acts like iodoacetate (Sorsby et al., 

 1957). These results provide indirect evidence that glycolytic inhibition is 

 the mechanism by which iodoacetate acts. It is perhaps pertinent to note 

 that the endocochlear application of iodoacetate decreases the microphonic 

 potentials in the cat (Bornschein and Thalmann, 1963). 



Single intravenous injections of iodoacetate (20-35 mg/kg), or two to 

 three injections (20 mg/kg) over a period of 24 hr, impair the ERG perma- 

 nently in rabbits and may selectively destroy the rod and cone cells. Karli 

 (1952) observed that several days after iodoacetate injection the rods are 

 severely affected, their nuclei pycnotic, and the chromatin condensed. 

 Following these visual cell changes, he found secondary modifications of 



