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Precursors to Anticholinergic toxicity

N Bodor
Retrometabolic drug design approaches incorporate targeting and metabolic considerations into the drug design process and represent a novel, systematic methodology for the design of safe, localized compounds. Two major design concepts aimed to increase the therapeutic index (the activity/toxicity ratio) of drugs were developed. Chemical delivery systems (CDS) are primarily used to allow targeting of the active biological molecules to specific target sites or organs based on predictable enzymatic activation...
July 1997: Die Pharmazie
M Contin, R Riva, F Albani, A Baruzzi
The current symptomatic treatment of Parkinson's disease mainly relies on agents which are able to restore dopaminergic transmission in the nigrostriatal pathway, such as the dopamine precursor levodopa or direct agonists of dopamine receptors. Ancillary strategies include the use of anticholinergic and antiglutamatergic agents or inhibitors of cerebral dopamine catabolism, such as monoamine oxidase type B inhibitors. Levodopa is the most widely used and effective drug. Its peculiar pharmacokinetics are characterised by an extensive presystemic metabolism, overcome by the combined use of extracerebral inhibitors of the enzyme aromatic-amino acid decarboxylase and rapid adsorption in the proximal small bowel by a saturable facilitated transport system shared with other large neutral amino acids...
June 1996: Clinical Pharmacokinetics
I P Lapin
Thirteen imipramine-like antidepressants and three anticholinergics potentiated yohimbine toxicity in mice. The strongest potentiation was observed after the nonantidepressant adrenergic compound AW 151129. Monomethyl derivatives were significantly stronger than their parent dimethyl compounds. Quaternary imipramine and amitriptyline, amphetamine, and inhibitors of monoamine oxidase were inactive. Pretreatment with an inhibitor of tyrosine hydroxylase (alpha-methyl-p-tyrosine) or the beta-adrenergic-blocking drug pindolol diminished lethality in mice treated with a combination of desmethylimipramine (AW 151129) and yohimbine...
1980: Psychopharmacology
J B Lassen, E Petersen, B Kjellberg, S O Olsson
The new 5HT-uptake inhibitor, FG 4963, and some tricyclic thymoleptics antagonized p-chloroamphetamine (PCA)-induced hypermotility in rats. FG 4963 was active in about the same s.c. and p.o. doses as chlorimipramine. FG 4963, imipramine and chlorimipramine potentiated hypermotility induced in mice by the 5HT precursor 5HTP, FG 4963 being slighly more active than chlorimipramine. In contrast to the tricyclic thymoleptics FG 4963 did not potentiate the heart rate increasing effect of NA in pithed rats. The peripheral anticholinergic effect of FG 4963 and of desipramine was almost identical while the other imipramine derivatives were more active...
May 1975: European Journal of Pharmacology
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