In vitro biological efficiency of tenocyclidine – TCP and its adamantane derivative TAMORF

Radić, Božica; Vrdoljak, Ana Lucić; Petek, Maja Jelena; Kopjar, Nevenka; Želježić, Davor

doi:10.1016/j.tiv.2006.07.002

Cited by 4 publications

(8 citation statements)

References 27 publications

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“…Since there are no published data on TCP genotoxicity in vivo, the second part of this study aimed to elucidate that subject. The results of our earlier in vitro study on human white blood cells suggest limited genotoxicity and promissing radioprotective properties of TCP (Radić et al, 2006). The present study reports for the first time the results concerning genotoxic and cytoprotective effects of TCP on rat blood and brain cells in vivo.…”

Section: Discussionsupporting

confidence: 57%

“…Previous studies revealed that both tested compounds exert various pharmacological effects by multiple mechanisms that are not related to AChE interactions (Škare et al, 2002;Ferle-Vidović et al, 1993;1995;Wang et al, 2004a;2004b;Radić et al, 2006). Since both TCP and TAMORF lack the oxime group, it is hard to believe that they can reactivate an already inhibited AChE, like oxime does (Radić et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

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Tenocyclidine treatment in soman-poisoned rats--intriguing results on genotoxicity versus protection.

Petek

Berend²,

Kopjar³

et al. 2008

Acta Biochim Pol

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This study aimed to evaluate the antidotal potency of tenocyclidine (TCP) that probably might protect acetylcholinesterase (AChE) in the case of organophosphate poisoning. TCP was tested alone as a pretreatment or in combination with atropine as a therapy in rats poisoned with (1/4) and (1/2) of LD(50) of soman. Possible genotoxic effects of TCP in white blood cells and brain tissue were also studied. Results were compared with previous findings on the adamantyl tenocyclidine derivative TAMORF. TCP given alone as pretreatment, 5 min before soman, seems to be superior in the protection of cholinesterase (ChE) catalytic activity in the plasma than in brain, especially after administration of the lower dose of soman. Plasma activities of the enzyme after a joint treatment with TCP and soman were significantly increased at 30 min (P

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Section: Discussionsupporting

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Tenocyclidine treatment in soman-poisoned rats--intriguing results on genotoxicity versus protection.

Petek

Berend²,

Kopjar³

et al. 2008

Acta Biochim Pol

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“…The general structure of the glucoconjugates is shown in Figure 3A. Tenocyclidine (TCP) and its adamantyl derivatives are studied as adjuvant antidotes to the oximes (12,13,14). Pretreatment with TCP or its adamantyl-morpholine derivative TAMORF ( Figure 3B) proved very effective against Soman when given to mice 15 min before Soman, followed by HI-6 (plus atropine) given 1 min after Soman.…”

Section: Synthesis Of Antidotes and Their In Vivo Testing In Experimementioning

confidence: 99%

Mechanisms of Organophosphate Toxicity and Detoxication with Emphasis on Studies in Croatia

Reiner

Radić

Simeon-Rudolf

2007

Archives of Industrial Hygiene and Toxicology

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This review comprises studies on the mechanisms of toxicity and detoxication of organophosphorus (OP) compounds done in Croatia in different research areas. One area is the synthesis of antidotes against OP poisoning and their in vivo testing in experimental animals. In vitro studies included in this review focus on the mechanisms of reversible inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), protection of cholinesterases from inhibition by OPs, and reactivation of phosphylated cholinesterases. The third area comprises distribution profiles of BChE and paraoxonase (PON) phenotypes in selected population groups and the detection of OPs and metabolites in humans. Finally, methods are described for the detection of OP compounds in human blood and other media by means of cholinesterase inhibition.

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“…Pretreatment with TAMORF protected animals from the lethal effects of soman and eliminated most of the soman-induced signs of toxicity in poisoned rats (2). Both TCP and TAMORF have shown low genotoxicity (2,17,18). Besides antidotal effi ciency, TCP and TAMORF showed interesting radioprotective properties (17).…”

mentioning

confidence: 99%

“…Both TCP and TAMORF have shown low genotoxicity (2,17,18). Besides antidotal effi ciency, TCP and TAMORF showed interesting radioprotective properties (17).…”

mentioning

confidence: 99%

Qualitative GC-MS Assessment of TCP and Tamorf Elimination in Rats

Petek¹,

Vrdoljak

Mršić³

2010

Archives of Industrial Hygiene and Toxicology

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Nerve agents are highly toxic organophosphorus (OP) compounds. They inhibit acetylcholinesterase (AChE), an enzyme that hydrolyses acetycholine (ACh) in the nervous system. Pathophysiological changes caused by OP poisonings are primarily the consequence of surplus ACh on cholinergic receptors and in the central nervous system. Standard treatment of OP poisoning includes combined administration of carbamates, atropine, oximes and anticonvulsants. In order to improve therapy, new compounds have been synthesised and tested. Tenocyclidine (TCP) and its adamantane derivative 1-[2-(2-thienyl)-2-adamantyl] morpholine (TAMORF) have shown interesting properties against soman poisoning. In this study, we developed a qualitative GC-MS method to measure elimination of TCP and TAMORF through rat urine in order to learn more about the mechanisms through which TCP protects an organism from OP poisoning and to determine the duration of this protective effect. GC-MS showed that six hours after treatment with TCP, rat urine contained only its metabolite 1-thienylcyclohexene, while urine of rats treated with TAMORF contained both TAMORF and its metabolites.

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In vitro biological efficiency of tenocyclidine – TCP and its adamantane derivative TAMORF

Cited by 4 publications

References 27 publications

Tenocyclidine treatment in soman-poisoned rats--intriguing results on genotoxicity versus protection.

Tenocyclidine treatment in soman-poisoned rats--intriguing results on genotoxicity versus protection.

Mechanisms of Organophosphate Toxicity and Detoxication with Emphasis on Studies in Croatia

Qualitative GC-MS Assessment of TCP and Tamorf Elimination in Rats

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