Oxotremorine, action

As with pilocarpine and arecoline, increased interest in pharmacotherapy of Alzheimer s disease and other memory deficit conditions has led to renewed and expanded studies of oxotremorine. This compound has little or no effect on serum or red cell but3nyl-cholinesterase. Oxotremorine has been described as a potent muscarinic partial agonist (172). However, an earlier report (11) presented evidence that oxotremorine has an indirect action in the CNS, perhaps by stimulation of choline acetyltransferase, resulting in elevation of acetylcholine levels. The peripheral actions of oxotremorine, including effects on cardiovascular mechanisms, have been ascribed (172) to preferential activation of M, receptors. Brimblecomb (211, 212) reported... 

If opiates and opiate peptides are acting on Ca + disposition they are not unique in this respect. Neurotransmitter release is known to be a Ca -dependent process, and, in fact a number of neurotransmitters or pharmacologic agents tors such as norepinephrine, adenosine and oxotremorine have been reported to act by inhibition of Ca + influx (123,125,126). This must mean that opiates produce their characteristic spectrum of effects, not because they have a unique mode of neuromodula-tory action, but because the receptors for the endogenous opiate ligands are located stratgetically at selective neuronal sites for the mediation of their specific effects. 

Nordstrom and coworkers showed that the analog of oxotremorine, A-methyl-A-(l-methyl-4-pyrrolidono-2-butynyl) acetamide, acts as a postsynaptic agonist in various muscarinic test models. However, this analog is also an antagonist of presynaptic muscarinic receptors. Such diversity in receptor action may contribute to the differences in overall activity of analogs in this series. 

In spite of the plethora of information on the structure-activity relationship in the oxotremorine series, the exact details on its mechanism of action are still unclear. 

The possible modes of action of amantadine and other drugs in parkinsonism are summarized in Table 1. Amantadine does not act like the centrally-acting anticholinergics In three animal preparations amantadine failed to cause anticholinergic effects (guinea pig ileum, acetylcholine-induced depressor effects in dogs, oxotremorine tremor in mice) ... 

New small animal methods, supplementing oxotremorine tremor, etc., have made possible study of adrenergic actions based mainly upon the changes in locomotor activity and stereotypy exerted by amphetamine and apomorphine and by drug effects upon turning behavior after striatal lesions caused by 6-hydroxydopamine, electrolysis and suction. 

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