Disease relevance of SKF-95282

• The present results are the first to demonstrate the existence of brain-penetrating antinociceptive agents chemically related to zolantidine and improgan, but further studies are needed to understand the mechanisms of both the pain relief and toxicity produced by these agents [1].
• The present study determined the effects of the brain-penetrating H2 receptor antagonist zolantidine (ZOL) on 2DG antinociception on the tail-flick and jump tests, as well as on 2DG hyperphagia, in rats [2].
• Neither mepyramine, an H1 receptor blocker nor zolantidine, an H2 blocker provided any decrease in brain swelling or water content [3].

Psychiatry related information on SKF-95282

• Chronic treatment with L-histidine (750 mg/kg) plus METH inhibited the METH-induced argumentation of stereotyped behavior, while that with FMH (100 mg/kg), pyrilamine (5 mg/kg) or zolantidine (5 mg/kg) potentiated it [4].
• In contrast, no significant influence on alpha-FMH-induced memory deficit was observed with zolantidine [5].
• One possibility is that zolantidine did not enter the brain in sufficient concentration to produce significant changes on sleep and wakefulness [6].
• The increase in the locomotor activity by thioperamide was blocked by i. p. pretreatment with (R)-alpha-methyl-histamine, an H3 agonist, or pyrilamine, an H1 antagonist, or zolantidine, an H2 antagonist [7].

High impact information on SKF-95282

• The HA-evoked increase in cAMP production in chick cerebral cortex was antagonized by selective H(2) receptor blockers (aminopotentidine >or= tiotidine > ranitidine >> zolantidine), and not significantly affected by mepyramine and thioperamide, selective H(1) and H(3) /H(4) receptor blockers, respectively [8].
• The action of zolantidine, a histamine H2-receptor antagonist which penetrates the brain, was characterized on the analgesia elicited by brief continuous footshock of 3 intensities [9].
• These results show that, despite the ability of zolantidine to inhibit HMT in vitro, large doses of this drug did not alter brain HA methylation or turnover in vivo, and they imply that blockade of post-synaptic H2-receptors does not change brain HA dynamics [10].
• 1. The novel benzthiazole derivative zolantidine (SK&F 95282) is a potent antagonist of histamine at H2-receptors in guinea-pig atrium and rat uterus [11].
• 5. Zolantidine is thus characterized as a potent selective brain-penetrating H2-receptor antagonist, and will be a valuable pharmacological tool for investigating possible physiological and pathological roles for histamine in the central nervous system [11].

Biological context of SKF-95282

• At the highest concentrations zolantidine also reduced basal heart rate and cardiac contractility [12].

Anatomical context of SKF-95282

• Moreover, co-administration of zolantidine dose-dependently increased morphine (10 mg/kg)-induced DA turnover in the limbic forebrain [13].
• The actions of zolantidine dimaleate and five other histamine H2 receptor antagonists, given into the lateral ventricle of rats, were assessed on nociceptive responses in the presence and absence of systemically administered morphine [14].
• In addition, zolantidine (1, 3 and 10 mg/kg) significantly increased DA turnover (DA ratio) in the limbic forebrain (nucleus accumbens and olfactory tubercle), implying that zolantidine may activate the mesolimbic DA system [13].
• Similar findings were obtained with another histamine H2-receptor blocker, zolantidine, which supposedly crosses the blood-brain barrier [15].
• The effects of the histamine H2 receptor blocker famotidine were investigated on the human isolated myocardium, in comparison with zolantidine, a new member of the same family [16].

Associations of SKF-95282 with other chemical compounds

• The effects of zolantidine, the first brain-penetrating H2-receptor antagonist, on the brain levels of histamine (HA) and the HA metabolite tele-methylhistamine (t-MH), the activity of histamine methyltransferase (HMT) and the brain HA turnover rates were investigated in rats [10].
• The histamine H1-receptor antagonist pyrilamine facilitated while the H2-antagonist zolantidine (5 mg/kg i.p) transiently decreased ripple occurrence [17].
• Pretreatment with the histamine-depleting agent alpha-fluoromethylhistidine (alpha-FMH, 50 mg/kg), the histamine H1 receptor antagonist pyrilamine (3 or 10 mg/kg), or the histamine H2 receptor antagonists cimetidine (100 mg/kg) and zolantidine (10 or 30 mg/kg) did not significantly modify nefopam antinociception in both tests [18].
• The effect of the new histamine H2-receptor antagonist zolantidine was studied in different cardiac and gastric H2-receptor assays in comparison with ranitidine [12].
• The effects of the H1-receptor antagonist diphenhydramine and the brain-penetrating H2-receptor antagonist zolantidine were studied in rats implanted for chronic sleep recordings [6].

Gene context of SKF-95282

• The H2 receptor antagonist zolantidine (0.3 mg/kg) significantly potentiated the morphine-induced place preference [13].
• Moreover, the improvement by thioperamide plus zolantidine was antagonized by pretreatment with histamine H1-receptor antagonists such as pyrilamine or ketotifen, but not by terfenadine [19].
• In a behavioral study, thioperamide (20 mg/kg) alone slightly ameliorated scopolamine-induced learning deficit, and pretreatment with zolantidine, a histamine H2-receptor antagonist, significantly enhanced the ameliorating effect of thioperamide [20].
• Different effects of the histamine H2 receptor blockers, famotidine and zolantidine, on the human atrium in vitro [16].
• The recent publications on the brain-penetrating H2 antagonist zolantidine and the selective H3 agonists and antagonists are expected to contribute to the knowledge of the histaminergic pathways in the brain [21].

Analytical, diagnostic and therapeutic context of SKF-95282

• Zolantidine inhibited the analgesia elicited by exposure to 3.5 mA for 3 min, with maximum inhibition observed 30 min after a dose of 5 mg/kg [9].

References