Physostigmine effectiveness

Carbamate Insecticides. These are stmcturaUy optimi2ed derivatives of the unique plant alkaloid physostigmine [57-47-6] a cholinergic dmg isolated in 1864 from Phjsostigma venenosum (see Alkaloids) (17,24,35—39). The carbamates maybe considered synthetic derivatives of the synaptic neurotransmitter acetylcholine, with very low turnover numbers. The A/,A/-dimethylcarbamates of heterocycHc enols (36) and the Ai-methylcarbamates of a variety of substituted phenols (35) with a wide range of insecticidal activity were described in 1954 (35). The latter are the most widely used carbamate insecticides, and the A/-methylcatbamates of oximes have subsequentiy been found to be effective systemic insecticides. 

The simpler substance apoharmine according to Flury causes increased reflex excitability in the dog. In the frog it produces a like effect which with larger doses goes on to tetanus. Esterification of harmol with methylcarbamic acid induces affinities with the physostigmine type of drug. ... 

The miotic effect induced by physostigmine lends itself to investigation of the interrelation of chemical constitution and pharmacological action, and Stedman has devoted much attention to this subject. Eseroline is devoid of miotic activity, so that the latter action in physostigmine must be mainly due to the fact that it is a methylurethane, and, since activity only becomes evident in the urethanes of phenolic bases or phenols with a basic side-chain, a basic nucleus for the urethanes appears also to be essential. 

Relative contraindications to the use of anticholinesterase treatment include a history of cardiovascular disease, asthma, glaucoma, and gastrointestinal or genitourinary obstruction. Symptomatic treatment of tachyarrhythmias with propranolol may be considered P blockers, however, are less effective than physostigmine. 

Released ACh is broken down by membrane-bound acetylcholinesterase, often called the true or specific cholinesterase to distinguish it from butyrylcholinesterase, a pseudo-or non-specific plasma cholinesterase. It is an extremely efficient enzyme with one molecule capable of dealing with something like 10000 molecules of ACh each second, which means a short life and rapid turnover (100 ps) for each molecule of ACh. It seems that about 50% of the choline freed by the hydrolysis of ACh is taken back into the nerve. There is a wide range of anticholinesterases which can be used to prolong and potentiate the action of ACh. Some of these, such as physostigmine, which can cross the blood-brain barrier to produce central effects and neostigmine, which does not readily... 

ACh is metabolised extraneuronally by the enzyme acetylcholinesterase, to reform precursor choline and acetate. Blocking its activity with various anticholinesterases has been widely investigated and some improvement in memory noted. Such studies have invariably used reversible inhibition because of the toxicity associated with long-term irreversible inhibition of the enzyme. Physostigmine was the pilot drug. It is known to improve memory in animals and some small effects have been seen in humans (reduces number of mistakes in word-recall tests rather than number of words recalled), but it really needs to be given intravenously and has a very short half-life (30 min). 

The limited effectiveness of physostigmine did, however, encourage the development of longer-acting orally effective anticholinesterases such as tacrine (tetrahydroamino-acrydine), velnacrine and donepezil. 

The effect of anisodine (91) on the release of acetylcholine has been investigated (211-213). Investigation of the pharmacological effects of anisodine (91) on the central nervous system in rabbits has shown a strong depressant effect (210). The effect was antagonized by physostigmine and... 

Ebert U, Oertel R, Wesnes K and Kirch W (1998). Effects of physostigmine on scopolamine-induced changes in quantitative electroencephalogram and cognitive performance. Human Psychopharmacology - Clinical and Experimental, 13, 199-210. 

D-tubocurarine from Chondrodendron tomentosum Ruiz et Pav. and Rauvolfia serpentina Benth. et Kurz and horse radish peroxidase 3 mg/ml, which prevent the peroxide formation, block the fruit formation as a whole, while yohimbine and gaillardine inhibit the seed formation. Neostigmine stimulates the fruit and seed yield, although its precursor physostigmine has no significant effect (Roshchina and Melnikova, 1998). 

Procedure Allelochemical and a compound belonging to natural artificial pesticides and medicinal drugs is preliminary added into the reaction media (see section Add). The difference in cholinesterase activity (measured as shown in sections 15.3) between a control (without the substance added) and the experimental variant is estimated. The results are compared with the effects of the cholinesterase inhibitors neostigmine and physostigmine. 

Kim Y-B, Cheon K-C, Hur G-H, Phi T-S, Choi S-J, Hong D, Kang J-G. Effects of combinational prophylactics composed of physostigmine and procyclidine on soman-induced lethality, seizures and brain injuries. Environ. Toxicol. Pharmacol. 11(1) 15-21,2002. 

Philippens IHCHM, Melchers BPC, Wolthuis OL. Active avoidance in guinea pigs, effects of physostigmine and scopolamine. Pharmacol. Biochem. Behav. 42 285-289, 1992. 

Philippens IHCHM, Olivier B, Melchers BPC. Effects of physostigmine on the startle in guinea pigs two mechanisms involved. Pharmacol. Biochem. Behav. 58 909-913, 1997. 

Philippens IHCHM, Busker RW, Wolthuis OL, Olivier B, Bruijnzeel PLB, Melchers BPC. Subchronic physostigmine pretreatment in guinea pigs effective against soman and without side effects. Pharmacol. Biochem. Behav. 59(4) 1061-1067, 1998. 

Philippens IHCHM, Groen B, Vanwersch RAP. Direct effects of physostigmine as a pretreatment in guinea pigs side effects and efficacy against soman. Proc.TG004 meeting, Medicine Hat, Canada, 2003. 

Van den Beukel I, van Kleef RGDM, Oortgiesen M. Differential effects of physostigmine and organophosphates on nicotinic receptors in neuronal cells of different species. NeuroToxicol. 19(6) 777-788, 1998. 

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