R. L. Metcalf

Salicylanilides: A New Group of Active Uncouplers of Oxidative Phosphorylation

Investigations using housefly mitochondria revealed several salicylanilide derivatives as the most effective uncoupling agents of oxidative phosphorylation reported so far. Even greater inhibition of the associated Pi-adenosine triphosphate exchange was shown with these compounds in both housefly and rat-liver mitochondria, and close similarity was observed between the two types of organelles.

Site of action of pharmacologically active compounds on the heart of Periplaneta americana L.

Denervation of the American cockroach heart leads to a simple myogenic heartbeat which is unresponsive to atropine, acetylcholine, and arecoline in concentrations up to 10−3 M, while the denervated heart responds by increasing its rate of rhythmic contraction when perfused with 5-hydroxytryptamine, d-tubocurarine, nicotine, tryptamine, DOPAmine, adrenalin, noradrenalin, and the carbamates m-isopropylphenyl-N-methyl carbamate (MIP) and 2-methyl-2-(methylthio) propionaldehyde-N-methyl carbamoyloxime (Temik). These responses support the contention that acetylcholine and atropine are acting on the cardiac nervous system, whereas the other compounds listed have an effect on the myocardium. The neurogenic classification of the cockroach heart requires re-examination. A more appropriate classification is myogenic with extensive nervous control.

The effects of cholinergic substances upon the isolated heart of Periplaneta americana

Abstract The effects of acetylcholine and twelve other structurally related esters in accelerating the heartbeat rate of the isolated heart of Periplaneta americana were studied. Acetylcholine was about forty times more effective than acetylthiocholine or any other analogues studied, indicating that the receptor sites are much more stereospecific than the active site of insect cholinesterase. Organophosphorus and phenyl N-methylcarbamate anticholinesterase at great dilutions also accelerate the rate of heartbeat. The importance of the acetylcholine cholinesterase system at the insect neural synapses is emphasized by the protective action afforded by pyridine aldoxime methiodide and atropine sulphate in antagonizing the action of the anticholinesterases on heartbeat rate.

Dieldrin susceptibility: partial restoration in Anopheles selected with a carbamate.

Selection of dieldrin-resistant Anopheles albimanus Wied. and normal Culex pipiens quinquefasciatus Say with m-isopropylphenyl methylcarbamate for 21 and 30 generations, respectively, resulted only in vigor tolerance to this and other aryl methylcarbamates. However, it caused substantial restoration of dieldrin- and DDT-susceptibility in Anopheles by increasing the frequency of homozygous susceptible phenotypes from 10 to 83 percent.