Nicotinic acetylcholine receptors: targets for commercially important insecticides

Millar, Neil S.; Denholm, I.

doi:10.1007/s10158-006-0040-0

Cited by 240 publications

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“…1) So far, several classes of insecticides targeting nAChRs have been developed and used worldwide for pest control. [2][3][4] Neonicotinoids acting on insect nAChRs are comparable with organophosphates and synthetic pyrethroids in terms of current market share. Targeting nAChRs raises concerns relating to mammalian toxicity, yet neonicotinoids show high selective toxicity to insects over vertebrates.…”

Section: Introductionmentioning

confidence: 99%

Potentiating and blocking actions of neonicotinoids on the response to acetylcholine of the neuronal .ALPHA.4.BETA.2 nicotinic acetylcholine receptor

et al. 2008

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Effects of imidacloprid, clothianidin, thiacloprid and related compounds on the acetylcholine (ACh)-induced response of the recombinant, expressed chicken a4b 2 nicotinic acetylcholine receptor (nAChR) were investigated using voltage-clamp electrophysiology. Imidacloprid and clothianidin enhanced the amplitude of the response to ACh of a4b 2 nAChR. In complete contrast, thiacloprid attenuated the amplitude of the response to ACh of a4b 2 nAChR. Replacing the nitro group of imidacloprid by a cyano group abolished the potentiating action, whereas exchanging the cyano group of thiacloprid for a nitro group conferred the ability to potentiate the ACh response. All three neonicotinoids shifted the ACh concentration-response curve without influencing the peak current amplitude of the ACh response.

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Section: Introductionmentioning

confidence: 99%

Potentiating and blocking actions of neonicotinoids on the response to acetylcholine of the neuronal .ALPHA.4.BETA.2 nicotinic acetylcholine receptor

et al. 2008

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“…As has been reviewed elsewhere, nAChRs have been implicated in several human neurological and psychiatric disorders [2][3][4] and are also an important target site for insecticides [5,6]. In both vertebrate and invertebrate species, nAChRs form a diverse family of receptors assembled from a wide range of subunit combinations [6,7].…”

Section: Introductionmentioning

confidence: 99%

“…Invertebrate species express a similarly diverse population of nAChRs, although less is know about their subunit composition [6,8].…”

Section: Introductionmentioning

confidence: 99%

“…Vertebrate muscle-type nAChRs have a subunit composition of either (α1)2β1γδ or (α1)2β1δε in fetal and adult muscle, respectively, whereas vertebrate neuronal nAChRs comprise a heterogeneous population of receptors of diverse subunit composition, assembled from α2-α10 and β2-β4 subunits [7] (note; the α8 subunit has been identified in avian but not in mammalian species). [6,[59][60][61]. For example, ten nAChR subunits (Dα1-Dα7 and Dβ1-Dβ3) have been cloned from the model insect species Drosophila melanogaster [62][63][64][65][66][67][68][69][70].…”

Section: Introductionmentioning

confidence: 99%

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A review of experimental techniques used for the heterologous expression of nicotinic acetylcholine receptors

Millar

2009

Biochemical Pharmacology

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Nicotinic acetylcholine receptors (nAChRs) are members of the Cys-loop family of neurotransmitter-gated ion channels, a family that also includes receptors for γ-aminobutyric acid, glycine and 5-hydroxytryptamine. In humans, nAChRs have been implicated in several neurological and psychiatric disorders and are major targets for pharmaceutical drug discovery. In addition, nAChRs are important targets for neuroactive pesticides in insects and in other invertebrates. Historically, nAChRs have been one of the most intensively studied families of neurotransmitter receptors. They were the first neurotransmitter receptors to be biochemically purified and the first to be characterized by molecular cloning and heterologous expression. Although much has been learnt from studies of native nAChRs, the expression of recombinant nAChRs has provided dramatic advances in the characterization of these important receptors. This review will provide a brief history of the characterization of nAChRs by heterologous expression. It will focus, in particular, upon studies of recombinant nAChRs, work that has been conducted by many hundreds of scientists during a period of almost 30 years since the molecular cloning of nAChR subunits in the early 1980's.

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“…[1][2][3][4][5][6][7][8][9][10] A prodrug is a substance that has to be transformed in order to show or enhance activity or to lessen unfavorable properties of the original ingredient. 11) Drabek and Neumann 12) introduced the term proinsecticide for an insecticide by referring to the pharmaceutical term.…”

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Proneonicotinoid

Kagabu

2011

J. Pestic. Sci.

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Since the discovery of imidacloprid in 1986, various structural modifications have been attempted to devise molecules with favorable biological properties different from those of the first product. [1][2][3][4][5][6][7][8][9][10] A prodrug is a substance that has to be transformed in order to show or enhance activity or to lessen unfavorable properties of the original ingredient. 11) Drabek and Neumann 12) introduced the term proinsecticide for an insecticide by referring to the pharmaceutical term. This article addresses nine prodrug types of the neonicotinoid, using the term proneonicotinoid in this context. Oxadiazine and Related Cyclic AzinesAcetal, thioacetal and aminal have been frequently used as a protective group for aldehyde or ketone in synthetic chemistry. 13) The assembled framework regenerates the carbonyl group by hydrolysis after the task, leaving the individual protecting fragments (Eq. 1, Fig. 1). Oxadiazine (XϭO), thiadiazine (XϭS) or triazine (XϭNMe) structure (1), constructed by linking both the amine ends of original insecticidal molecule (2) with formaldehyde through the corresponding hetero fragment, can be viewed as a similar assembly. 14-16) The cleavage of thiamethoxam (3) into clothianidin (5) in insects and plant tissues has been reported. 17,18) Hydrolysis comparison of the three cyclic azines (1) to the corresponding diaminonitroimines (2) in a physiological salt solution showed that the half-lives of the oxadiazines were notably longer than the corresponding thiadiazines and triazines. We have attributed the stability of the oxadiazine framework to the relatively strong -NCH 2 -O-CH 2 N-linkage by comparing the bond energy for C-O of 85-91 kcal/mol with 61 kcal/mol for C-S and 69-75 kcal/mol for C-N. 19) Thus, the devised thiamethoxam displays several favorable profiles in field practice, 16) and its present sales volume worldwide ranks second in the neonicotinoid class. This prodrug development practice clearly shows that a small structural variant (only one atom in this case) leads to large differences in the success. Mannich BasesThe Mannich reaction is the condensation of a labile C-H bond with an aldehyde and a primary or secondary amine to form a so-called Mannich base. 20) This well-established synthetic protocol was applied to a proneonicotinoid construction (Eqs. 2-4, Fig. 2). 21,22) The Mannich bases (7a, b) derived from b ,b -diamino nitroethylene molecules (6a, b) can regenerate the parent component in an acidic milieu. The concentrations of Mannich bases (7a, b) to cause spontaneous neuroblocking in the excised central nerve cord of American cockroaches (Periplaneta americana L.) were 100-140 mM at the level of 140 mM of 3N-Me (6c) derivative, and far higher than the 1.6-1.9 mM of the starting molecules (6a, b). However, 24 hr after the injection the minimum lethal doses were ProneonicotinoidShinzo KAGABU* Department of Chemistry, Faculty of Education, Gifu University, Gifu 501-1193, Japan (Received January 5, 2011 Accepted February 18, 2011) Prodrug is a biologi...

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Nicotinic acetylcholine receptors: targets for commercially important insecticides

Cited by 240 publications

References 130 publications

Potentiating and blocking actions of neonicotinoids on the response to acetylcholine of the neuronal .ALPHA.4.BETA.2 nicotinic acetylcholine receptor

Potentiating and blocking actions of neonicotinoids on the response to acetylcholine of the neuronal .ALPHA.4.BETA.2 nicotinic acetylcholine receptor

A review of experimental techniques used for the heterologous expression of nicotinic acetylcholine receptors

Proneonicotinoid

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