Anti-inflammatory properties of CB1-receptor antagonist involves beta2 adrenoceptors.

Antagonists of the cannabinoid receptor 1 (CB1) impart anti-inflammatory activity even though, paradoxically, CB2 receptors are more predominant on cells of the immune system. We attempted to understand the mechanism of this activity by using an acute model of lipopolysaccharide-induced inflammation/stress in both rat and mouse, with selective antagonists to CB1 receptors. We demonstrate that the ability of a CB1 antagonist to inhibit release of proinflammatory cytokines is not dependent on either adrenal-derived catecholamines or corticosteroids or input from the pituitary or thymus glands but does involve the spleen.

CJ-13610, an orally active inhibitor of 5-lipoxygenase is efficacious in preclinical models of pain.

Zileuton, a redox and iron chelator 5-lipoxygenase (5-LOX) inhibitor and, leukotriene receptor antagonists are presently used clinically in the long term treatment of asthma. Recent data implicate 5-LOX pathway in pain signaling. We report 5-LOX expression in the central nervous system (CNS) and analyze the pain efficacy of a new class of non redox, non iron chelating 5-LOX inhibitor.

The CB1 receptor antagonist SR141716 enhances stimulus-induced activation of the primary somatosensory cortex of the rat.

Several recent studies have demonstrated a neuromodulatory role for endocannabinoids via their ability to act as retrograde inhibitors of synaptic neurotransmission. We utilized the functional hyperemic response to controlled whisker stimulation to determine whether endogenous cannabinoids modulate synaptic transmission within the primary somatosensory cortex of rats. As previously demonstrated, whisker-stimulation resulted in a robust hyperemic response measured using laser Doppler flowmetry within the whisker barrel cortex.