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Adamantyl tenocyclidines - adjuvant therapy in poisoning with organophosphorus compounds and carbamates (CROSBI ID 95477)

Prilog u časopisu | izvorni znanstveni rad | međunarodna recenzija

Škare, Danko ; Radić, Božica ; Lucić, Ana ; Peraica, Maja ; Domijan, Ana-Marija ; Milković-Kraus, Sanja ; Bradamante, Vlasta ; Jukić, Ivan Adamantyl tenocyclidines - adjuvant therapy in poisoning with organophosphorus compounds and carbamates // Archives of toxicology, 76 (2002), 3; 173-177-x

Podaci o odgovornosti

Škare, Danko ; Radić, Božica ; Lucić, Ana ; Peraica, Maja ; Domijan, Ana-Marija ; Milković-Kraus, Sanja ; Bradamante, Vlasta ; Jukić, Ivan

engleski

Adamantyl tenocyclidines - adjuvant therapy in poisoning with organophosphorus compounds and carbamates

Organophosphates (OPs) and carbamates exhibit their toxicity by inhibiting acethylcholinesterase (AChE, EC 3.1.1.7) due to phosphorylation, or carbamylation in case of carbamate poisoning. OP poisoning is treated by atropine (muscarinic cholinergic receptor antagonist) and cholinesterase reactivators - oximes (PAM-2Cl, TMB-4, and HI-6). In contrast to the irreversible inhibition of AChE by OPs, carbamylated enzyme reactivates rapidly and antidotal treatment is limited to atropine. The objective of this study was to evaluate the efficiency of thienyl phencyclidine (tenocyclidine, TCP) and its new synthesized adamantyl derivatives containing piperidine (TAPIP), pyrolidine (TAPIR) and morpholine (TAMORF) group in mice poisoned with OPs and carbamates. These new compounds were characterized by m.p. determination, elemental analysis, and spectroscopic methods (IR, 1H-NMR, 13C-NMR, MS). They showed low acute toxicity (LD50), and their LD50 values varied from 106.00 mg kg -1 b.m. (TCP) to >504.00 mg kg -1 b.m. (TAMORF). TCP and its adamantyl derivatives were administered intraperitoneally (2.5 mg kg-1 b.m.) together with atropine (10.0 mg kg-1 b.m.) and with or without 1/4 LD50 of HI-6. Each compound administered with atropine had a therapeutic effect in the poisoning with carbamates propoxur, aldicarb, and Ro 02-0683 (therapeutic dose was from 3.18 LD50 of aldicarb to 16.00 LD50 for propoxur). However, the efficiency of those compounds in combination with atropine was lower in poisoning with OP insecticide dichlorvos (DDVP) and warfare agents soman and tabun. In soman-poisoned mice the best therapeutic effects were obtained with the combination of HI-6 plus atropine and tested compounds, which ensured the survival of all treated animals with 4.00-6.40 LD50 of soman. The results suggest that TCP and adamantyl tenocyclidines could be used in combination with atropine as antidotes in carbamate poisoning and as adjuvant therapy to HI-6 and atropine in soman poisoning.

Adamantanes; Tenocyclidines; Atropine; HI-6; Carbamates; Organophosphorus compounds

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Podaci o izdanju

76 (3)

2002.

173-177-x

objavljeno

0340-5761

Povezanost rada

Kliničke medicinske znanosti

Indeksiranost