Curarizing effects

The genus Malouetia occurs in both Africa and South America. It is distinguished by the same types of alkaloids as Funtumia and Holarrhena. Of particular interest is the isolation of the quaternary alkaloid malouet-ine with curarizing effect in the African Malouetia, bequaertiana Woods. It is probable that the same effect produced by the Venezuelan drug guachamacd can be attributed to some alkaloids of the South American Malouetia (3). 

Pharmacology of Calabash-curare.f —Paralytic Activity. A number of Strychnos alkaloids have considerably greater paralytic action than any previously known natural or synthetic neuromuscular blocking agent. Unfortunately, frogs are not suitable for the evaluation of curare effects because they show sea-... 

As early as 1811, Brodie (2) observed that curare effected respiration in warm-blooded animals and that death was due to respiratory failure, and, several years later, Bernard (3) described the location of the physiological action as being at the junction of the nerve and muscle (myoneural junction). Bernard s classical experiments showed that curare blocked the transmission of impulses from nerve to muscle without apparent effects on either the nerve trunk or the muscle fibers themselves. He found that direct stimulation of a curarized muscle produces a contraction. 

Quinine (66) is toxic to many bacteria and unicellular organisms. This alkaloid is active against Trypanosoma cruzi (Wink, 1993). Quinine is a local anesthetic and has cardiovascular effects, oxytocic effects, curarizing effects, and an analgesic effect comparable to salicylate. Quinine is not commonly used alone as an antimalarial today (Cordell,... 

Similar types of alkaloids have been isolated from the plants of the closely related species such as Funtumia and Malouetia. It is interesting to note that an alkaloid isolated from the wood of an African Malouetia was reported to possess a curarizing effect (87). 

Canadine is bitter and in small doses causes drowsiness and depression. In large doses it gives rise to transient excitement succeeded by depression and paralysis of the central nervous system. Its injection is followed by violent peristalsis with diarrhoea. It is said to have no effect on the blood pressure. The pharmacological action of canadine a- and -meihochlorides was examined by Laidlaw, who found both to have the curare-like action common to ammonium bases, the -isomeride being the more active the relative activities of the four optically active forms are given as h da. ip dp = 1 Q 2 28. 

Following his extensive studies of nicotine, curare, and other chemicals acting on what is now known as the cholinergic nervous system, John Langley hypothesized that there must be receptive substances present in cells to explain the effects of nicotine alone and in combination with other chemicals. He wrote Since the accessory substance is the recipient of stimuli which it transfers to the contractile material, we may speak of it as the receptive substance (italics in original) of the muscle (Langley 1905). These conclusions followed from observations... 

The effect of administering different botulinum neurotoxin serotypes at the same time or within several months of each other is unknown. Excessive neuromuscular weakness may be exacerbated by administration of another botulinum toxin prior to the resolution of the effects of a previously administered botulinum toxin. Aminoglycosides Cautiously perform coadministration of botulinum toxin type A and aminoglycosides or other agents interfering with neuromuscular transmission (eg, curare-like nondepolarizing blockers, lincosamides, polymyxins, quinidine, magnesium sulfate, anticholinesterases, succinylcholine chloride) because the effect of the toxin may be potentiated. 

Neuromuscular blockade Neurotoxicity can occur. Aminoglycosides may aggravate muscle weakness because of a potential curare-like effect on the neuromuscular junction. 

Mecfianism of Action A cinchona alkaloid that relaxes skeletal muscle by increasing the refractory period, decreasing excitability of motor end plates (curare-like), and affecting distribution of calcium with muscle fiber. Antimalaria Depresses oxygen uptake, carbohydrate metabolism, elevates pH in intracellular organelles of parasites. Therapeutic Effect Relaxes skeletal muscle produces parasite death. Pharmacokinetics Rapidly absorbed mainly from upper small intestine. Protein binding 70%-95%. Metabolized in liver. Excreted in feces, saliva, and urine. Half-life 8-14 hr (adults), 6-12 hr (children). 

Receptor interactions were seen at nicotinic and muscarinic receptors. No correlations were found, however, between atropinelike or curare-like actions of these compounds and their protective effects against organophosphate poisoning. 

Wagley48 found that V produced a dose-related decrease in the endplate potential of the curarized iliofibularis muscle of the frog at 1-3 x 10 2 m. A similar effect of 2-PAM I was found at 1-3 x 10-3 M, whereas concentrations below 10 3 M produced dose-related increases in the endplate potential. Fleisher et al.47 found that III, unlike I, had no excitatory action on the Isolated frog rectus abdominis, but had a more potent effect than I in inhibiting the response of that muscle to decamethonlum, carbamylcholine, and acetylcholine. 

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