We have recently identified 1,8-naphthyridin-2(1H)-one-3-carboxamide as a new scaffold very suitable for the development of new CB2 receptor potent and selective ligands. In this paper we describe a number of additional derivatives in which the same central scaffold has been variously functionalized in position 1 or 6. All new compounds showed high selectivity and affinity in the nanomolar rang...

We have previously reported that mild TBI created by focal left-side cranial blast in mice produces widespread axonal injury, microglial activation, and a variety of functional deficits. We have also shown that these functional deficits are reduced by targeting microglia through their cannabinoid type-2 (CB2) receptors using 2-week daily administration of the CB2 inverse agonist SMM-189. CB2 in...

The use of cannabis can impair cognitive function, especially short-term memory. A controversial question is whether long-term cannabis use during the late-adolescence period can cause irreversible deficits in higher brain function that persist after drug use stops. In order to examine the short- and long-term effects of chronic exposure to cannabinoids, rats were administered chronic i.p. trea...

The ECS (endocannabinoid system) plays an important role in the onset of obesity and metabolic disorders, implicating central and peripheral mechanisms predominantly via CB1 (cannabinoid type 1) receptors. CB1 receptor antagonist/inverse agonist treatment improves cardiometabolic risk factors and insulin resistance. However, the relative contribution of peripheral organs to the net beneficial m...

It is well accepted that endogenous cannabinoids and CB1 receptors are involved in the regulation of smooth muscle contractility and intestinal motility, through a mechanism mainly related to reduction of acetylcholine release from cholinergic nerve endings. Because, few data exist on a possible modulatory action of the cannabinoid agents on the non-adrenergic non-cholinergic (NANC) excitatory ...

The effects of psychoactive substances from marihuana (Cannabis sativa/indica, Lam.) are known for a long time, but the pharmacological mechanisms of them are not uncovered in details yet. Most of cannabinoid actions are evoked by interaction with specific CB1 or CB2 cannabinoid receptors (CB). CB1 receptors are localized predominantly in the central and peripheral nervous systems while CB2 rec...

Endocannabinoid (ECB) system plays a vital role in responses to stress. Moreover, ECB and its receptors cause anti-inflammatory, anti-oxidative and neuroprotective effects by modulating neuronal, glial and endothelial cell functions. A number of studies have demonstrated ECB system notably defects in neurotraumatic and neurodegenerative diseases like epilepsy, TBI, Alzheimer’s disease and...

BACKGROUND AND PURPOSE We have previously reported the development of CB-25 and CB-52, two ligands of CB1 and CB2 cannabinoid receptors. We assessed here their functional activity. EXPERIMENTAL APPROACH The effect of the two compounds on forskolin-induced cAMP formation in intact cells or GTP-gamma-S binding to cell membranes, and their action on nociception in vivo was determined. KEY RESU...

Background and purpose: Cannabis is the source of at least seventy phytocannabinoids. The pharmacology of most of these has been little investigated, three notable exceptions being D9-tetrahydrocannabinol, cannabidiol and D9-tetrahydrocannabivarin. This investigation addressed the question of whether the little-studied phytocannabinoid, cannabigerol, can activate or block any G protein-coupled ...