1 The hypotensive effect of imidazoline-like drugs, such as clonidine, was attributed both to alpha2-adrenergic receptors and nonadrenergic imidazoline receptors, which are divided into I1, I2 and I3 subtypes. 2 We have recently synthesized a derivative of (2-(2-chloro-4-iodo-phenylamino)-5-methyl-pyrroline (LNP 911), the first high-affinity and selective ligand for I1 receptors (I1R), with a p...

Compounds with an imidazoline or guanidinium moiety elicit a variety of stimulatory and inhibitory cell responses in both central and peripheral tissues. Many of these effects are mediated by interaction with alpha-adrenergic receptors, but these molecules also selectively recognize other membrane-bound proteins with high affinity. We used a functionalized derivative of the imidazoline molecule...

Radioligand binding experiments were carried out to identify and characterize nonadrenoceptor [H]idazoxan binding sites and [H](1,2-di-(2-tolyl)guanidine) binding sites in the rat and human stomach. Furthermore, we examined two selected aspects of their potential functional significance. Binding of [H]idazoxan (Kd 5 11.1 nM and 12.4 nM, respectively) and [H]DTG (Kd 5 932 nM and 242 nM, respecti...

BACKGROUND Moxonidine, a novel imidazoline-alpha2-adrenergic receptor-selective analgesic, was recently identified as antinociceptive but has yet to be evaluated in neuropathic pain models. alpha2-adrenergic receptor-selective analgesics, and high-efficacy opioids, effectively inhibit neuropathic pain behaviors in rodents. In contrast, morphine potency and efficacy decreases in states of neurop...

The cellular mechanisms that underlie the enhancement of clonidine-evoked hypotension in aortic barodenervated (ABD) rats and its dependence on central adenosine A(2A) receptor (A(2A)R) are not known. We tested the hypothesis that A(2A)R-mediated phosphorylation of extracellular signal-regulated kinase (pERK)1/2 in the rostral ventrolateral medulla (RVLM) and its downstream activation of nitric...

This study examined whether a novel imidazoline I₂ receptor ligand CR4056 could serve as a discriminative stimulus and whether it shares similar discriminative stimulus effects with other reported I₂ receptor ligands. Eight male Sprague-Dawley rats were trained to discriminate 10.0 mg/kg CR4056 (i.p.) from vehicle in a two-lever food-reinforced drug discrimination procedure. Once rats acquired ...

It has been shown in various mammal species that clonidine, a well known centrally acting hypotensive agent, acts through the activation of imidazoline receptors (IRs) in the nucleus reticularis lateralis (NRL) of the brainstem. Specific binding sites sensitive to imidazolines and insensitive to catecholamines have been detected in rat and bovine, as well as human brains. An endogenous ligand, ...

It is generally thought that the cardiovascular and renal effects of clonidine, an alpha-2 adrenergic agonist, are mediated by central mechanisms. Our previous work has shown that diuresis and natriuresis caused by central administration of clonidine are mediated by an enhanced release of atrial natriuretic factor (ANF). Because clonidine has been shown to have peripheral actions the objective ...

The imidazoline system (a concept which is barely over decades old) consists in imidazoline receptors I, I2 and I3 and their active endogenous ligands, the most important of which is agmatine. Brain contains both I1 and 12 of imidazoline receptors. One of the most important functions of this system is modulation of different behaviour components, such as suicidal behaviour, stress, anxiety, foo...