Prolongation of Cocaine Effect

Herschman, Zvi; Aaron, Cynthia K.

doi:10.1097/00000542-199103000-00041

Cited by 13 publications

(5 citation statements)

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“…This fact is also observed in humans and is extremely relevant for anesthesia. The potency of cocaine in humans and lethality in mice are enhanced by OP pesticide BuChE inhibition (Herschman et al, 1991;Hoffman et al, 1992). The functions of BuChE will be better understood when it is possible to study BChE-deficient mice, but it is already evident that it serves as a possible peripheral target in OP poisoning and as a scavenger in reducing OP toxicity.…”

Section: Cholinesterases Ache and Buchementioning

confidence: 99%

New insights on molecular interactions of organophosphorus pesticides with esterases

et al. 2017

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Organophosphorus compounds (OPs) are a large and diverse class of chemicals mainly used as pesticides and chemical weapons. People may be exposed to OPs in several occasions, which can produce several distinct neurotoxic effects depending on the dose, frequency of exposure, type of OP, and the host factors that influence susceptibility and sensitivity. These neurotoxic effects are mainly due to the interaction with enzyme targets involved in toxicological or detoxication pathways. In this work, the toxicological relevance of known OPs targets is reviewed. The main enzyme targets of OPs have been identified among the serine hydrolase protein family, some of them decades ago (e.g. AChE, BuChE, NTE and carboxylesterases), others more recently (e.g. lysophospholipase, arylformidase and KIA1363) and others which are not molecularly identified yet (e.g. phenylvalerate esterases). Members of this family are characterized by displaying serine hydrolase activity, containing a conserved serine hydrolase motif and having an alpha-beta hydrolase fold. Improvement in Xray-crystallography and in silico methods have generated new data of the interactions between OPs and esterases and have established new methods to study new inhibitors and reactivators of cholinesterases. Mass spectrometry for AChE, BChE and APH have characterized the active site serine adducts with OPs being useful to detect biomarkers of OPs exposure and inhibitory and postinhibitory reactions of esterases and OPs. The purpose of this review is focus specifically on the interaction of OP with esterases, mainly with type B-esterases, which are able to hydrolyze carboxylesters but inhibited by OPs by covalent phosphorylation on the serine or tyrosine residue in the active sites. Other related esterases in some cases with no-irreversible effect are also discussed. The understanding of the multiple molecular interactions is the basis we are proposing for a multi-target approach for understanding the organophosphorus toxicity.

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Section: Cholinesterases Ache and Buchementioning

confidence: 99%

New insights on molecular interactions of organophosphorus pesticides with esterases

et al. 2017

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“…Illicit cocaine users with severe toxicity were found to have 15 to 25% lower mean BChE activity compared with nonusers or users without complications (Devenyi, 1989;Hoffman et al, 1992;Om et al, 1993). Addicts have deliberately inhibited BChE with organophosphate pesticides in an attempt to prolong the cocaine "high" (Herschman and Aaron, 1991). Furthermore, there is some evidence from in vitro and animal studies that administration of exogenous BChE may help in the management of cocaine toxicity and addiction (Browne et al, 1998;Carmona et al, 1998Carmona et al, , 2000.…”

Section: Cocainementioning

confidence: 99%

Pharmacogenetics, Drug-Metabolizing Enzymes, and Clinical Practice

2006

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“…Animals with inhibited BChE are of enhanced sensitivity to succinylcholine, mivacurium, and aspirin (71). The potency of cocaine in humans and lethality in mice is enhanced by OP pesticide inhibition of BChE (72,73). BChE as a detoxifying enzyme administered iv decreases the lethality of sarin and the toxicity of cocaine (74,75).…”

Section: Bchementioning

confidence: 99%