NAChR agonistic action

On the other hand, a so-called cleavage of the imidazolidine 5-ring of 7 led to the efficacy of the open-chain 12, which is higher than that of ACh or 7 on the SADyS2 hybrid nAChR expressed in X. oocytes. The super agonist action of 12 and related ligands may account for the more potent action of 12 than that of 7 on a wide range of insect pests [200]. 

Nicotine is an agonist at the nicotinic acetylcholine receptor (nAChR) 921 The ventral tegmental area (VTA) is a critical site for nicotine action 921... 

The agonist radioligands [ HJnicotine and [ HJepibatidine, which are most commonly used to monitor nAChR numbers, freely cross lipid bilayers. Therefore, they do not discriminate between intracellular and surface nAChRs and the majority of the increase in high-affinity binding sites appears to be intracellular (Whiteaker et al. 1998 Vallejo et al. 2005). It is now appreciated that nicotine can accumulate within cells and a new consensus is emerging that supports an intracellular action of nicotine that enhances assembly and/or maturation of nAChRs (Nashmi et al. 2003 Darsow et al. 2005 Kuryatov et al. 2005 Sallette et al. 2004, 2005 Nashmi and Lester 2007 Fig. 4). 

Nicotine Nicotiana tabacum L.) (11), an agonist of the nicotinic-type acetylchoUne receptor (nAChR), has long been known for its mechanism of action. Nicotine-like compounds offer much potential in the treatment... 

Nicotine is an agonist to the neuronal nicotinic acetylcholine receptors (nAChR). These receptors are the likely site at which nicotine exerts its central actions. Evidence supports the involvement of the central nAChR in neurotransmitter release (195), and a large body of evidence indicates that dopamine release from dopaminergic neurons is mediated by activation of the brain nAChRs (196). It has also been shown that both nicotinic receptors and muscarinic receptors in the ventral tegmental area (VTA) activate the dopaminergic neurons and thus play a role in the reward effect of nicotine (197). In addition, animal data sug-... 

As mentioned above, galantamine has two basic mechanisms of action. It reversibly inhibits cholinesterases, being approximately 50-fold more potent as an AChE inhibitor than a BuChE inhibitor. It also interacts directly with nAChRs, potentiating their activation by subsaturating concentrations of classical agonists (Pereira et al., 2002). 

In insects, genes are identified encoding multiple uAChR subunits, suggesting the existence of diverse insect receptor subtypes. As an agonist-gated ion channel complex for rapid excitatory neurotransmission, the nAChR is widely distributed in insect CN S and constitutes a major target for insect action. However, the functional architecture and diversity of insect nAChRs are poorly understood compared with their vertebrate counterparts [91]. In general, insect nAChRs are diverse in structure, as are those from vertebrates. 

Neonicotinoids are insecticides acting on insect nAChRs (1). For a long time they are very effective on commercially important Hemipteran pest species such as aphids, whiteflies and planthoppers, but also control Coleopteran and some Lepidopteran pests (/). The biochemical mode of action (MoA) of neonicotinoids has been studied and characterized extensively in the past 10 years. Ail neonicotinoids act selectively as agonists at the insect nAChRs and they are part of a single MoA group as defmed by the Insecticide Resistance Action Committee (IRAC an Expert Conunittee of Crop Life) for resistance management purposes (2). Today the neonicotinoids are ... 

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