HGG12 and HGG42 are effective therapeutic agents in experimental organophosphate poisoning even after "aging" of the phosphonylated cholinesterase (Hauser, Kirsch, Weger, 1981). In this study we investigated their action in the isolated superior cervical ganglion of the rat (SCGR) after cholinesterase inhibition by Soman (.4 microM). As these two compounds have ganglion blocking properties (Kirsch, Weger, 1981), the action of hexamethonium bromide (C6) and atropine was also investigated and compared to theirs. The typical effects of Soman in the SCGR are a block of ganglionic transmission within 10 sec in a test train of stimuli of 6 Hz, 30 sec, and an increase of the NAD(P)H-fluorescence response up to 3 times the control value. Addition of HGG12 or HGG42 in a concentration of 30-60 microM restores transmission and decreases the metabolic response to almost normal values while obidoxime (60 microM) has no effect at all. C6 (117 microM) and to a lesser degree atropine (30-60 microM) also improve ganglionic transmission and the metabolic response in cholinesterase poisoning. The pattern of amplitudes of APs in a test train of stimuli however is only restored by the HGG compounds and a comparison of equipotent concentrations (50% inhibition of AP in unpoisoned ganglia) shows that HGG12 has the best effects in Soman poisoned SCGR. The superiority of HGG12 can be explained by an inhibitory action of HGG12 on both nicotinic and muscarinic ganglionic receptors.

Action Potentials↗

PubMedDate not supplied

Effects of 4-dimethylaminophenol in rat kidneys, isolated rat kidney tubules and hepatocytes.

1. Addition of 4-dimethylaminophenol (DMAP) to suspensions of isolated rat kidney tubules increased extracellular lactate dehydrogenase (LDH) at concn. which did not markedly affect gluconeogenesis. ATP content was also decreased by DMAP but this did not occur until the membrane became permeable to LDH. There was no similar leakage of the mitochondrial enzyme glutamate dehydrogenase. 2. After i.v. injection of DMAP to rats in doses which did not inhibit gluconeogenesis, kidney glutathione was decreased and the urinary LDH was increased. DMAP was irreversibly bound to tissue in rat, with the highest binding in the kidney. The highest binding occurs in those tissues in which DMAP causes necrosis. 3. In isolated rat hepatocytes, DMAP caused toxic effects which were similar but less extensive than occur on addition of DMAP to kidney tubules. The formation of acid-soluble metabolites was higher in isolated rat hepatocytes (20 nmol/mg protein) than in rat kidney tubules (4 nmol/mg protein). DMAP-glucuronide and DMAP-sulphate comprised the major acid-soluble metabolites in both preparations; conjugates of DMAP with glutathione or cysteine were also found.

Adenosine Triphosphate↗

PubMedDate not supplied

[A case of vaginal cyanide administration].

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Adult↗