Paralytic activity

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-... 

There is a wide variation in the paralytic activity of calabash alkaloids. In Figure 2 the limits of the different areas on the abscissa represent the head-drop and the minimal lethal dose for mice the ordinate indicates the duration of paralysis caused by an intermediate dose (logarithmic scale). Seven alkaloids are found to be more active than d-tubocurarine (291) of these C-toxiferine (38) is extremely potent. The lethal doses of two alkaloids, C-alkaloid G (56) and C-alkaloid E (51), are less than 1 fig per kg, indicating that their potency is 100 times greater than that of d-tubocurarine (291). 

In the 1980s, our group began to screen microbes for insecticidal compounds that could be used in practice, or become lead compounds for the generation of new carbon skeletons. As a result, various strains were found to exhibit insecticidal, convulsive and paralytic activities against silkworms. This chapter deals with the procedures used for isolation of bioactive strains and their active principles. An overview of their chemical structures, activities, synthesis, and structurally related compounds is also given. 

Death from overdose of barbiturates may occur and is more likely when more than 10 times the hypnotic dose is ingested. The barbiturates with high lipid solubility and short half-lives are the most toxic. Thus the lethal dose of phenobarbital is 6—10 g, whereas that of secobarbital, pentobarbital, or amo-barbital is 2-3 g. Symptoms of barbiturate poisoning include CNS depression, coma, depressed reflex activity, a positive Babinski reflex, contracted pupils (with hypoxia there may be paralytic dilation), altered respiration, hypothermia, depressed cardiac function, hypotension, shock, pulmonary complications, and renal failure. 

The a -, /z-, and a-conotoxins are the best characterized of the peptides isolated from Conus venoms so far. However, a large number of other peptides are found in these venoms. These comprise both paralytic toxins to immobilize the prey of the cone snail, and other biologically active peptides which are not themselves directly paralytic. Only the briefest overview of these peptide components will be presented here. 

A large number of other non-paralytic but biologically active peptides have been purified and sequenced. In most cases however, the detailed mechanism of action has not yet been elucidated. Clearly, Conus venoms will be a rich source of such peptides that can be used to probe various receptor targets, particularly in the central nervous system. 

Very rapid-acting paralytic neurotoxin that binds to sodium channels of nerve and muscle cells depolarizing neurons by increasing the sodium channel permeability. It is obtained from South American poison-dart frogs (Phyllobates aurotaenia, Phyllobates terribilis). It is insoluble in water but soluble in hydrocarbons and other nonpolar solvents. The dried toxin can remain active for at least a year. However, it is relatively nonpersistent in the environment. 

Incidents of vincristine overdosage have been reported relatively frequently in the medical literature. Some of these have involved inadvertent administration of the intravenous formulation into the central nervous system by the intrathecal route this produces devastating results by a combination of chemical damage to sensitive neuronal tissue as well as biochemical perturbations. Two representative cases of vincristine overdose were described (46) involving administration of vincristine to patients scheduled to receive vinblastine. In one patient toxicity initially involved vomiting and diarrhea with subsequent constipation and paralytic ileus (inhibition of motor activity in the small intestine). Muscle pain... 

Biologically active isobutylamides have been isolated from plants of the Compositae and the Rutaceae. Some of the isohutyla-mides were found to have paralytic and toxic activities against insects, especially when applied topically to several species of Coleopterans and Dipterans.The present work describes the isolation, spectral identification, synthesis, and insect and snail bioassays of five isobutylamides from the Rutaceae plant, Fagara macrophylla. In addition, the synthesis and bioassay of four analogs of the isbbutylamide natural products are described. 

The pharmacological properties of P-erythroidine and its dihydro derivative are very similar to those of d-tubocurarine and therefore need not be described in any detail. The two compounds differ from curare in three important respects, namely, less potent paralytic action on neuromuscular junctions, briefer duration of paralysis, and oral efficacy. Indeed, gastrointestinal absorption of the alkaloids is so rapid and complete that the difference between effective oral and subcutaneous doses is rather small. Dihydro-P-erythroidine is longer acting than P-erythroidine and about six times as active. Similar to curare, P-erythroidine and its dihydro derivative are antagonized at the neuromyal junction by anticholinesterases such as neostigmine. 

Phaeantharine Mosquito larvicide paralytic in mammals and quail moderate activity against gram-positive bacteria (Bacillus subtilis, S. aureus) 8... 

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