Risperidone suppresses caffeine-induced hyperthermia and hyperactivity in rats.

Caffeine, a methylxanthine alkaloid, works as a nonselective adenosine receptor antagonist. It is the most widely used psychostimulant drug worldwide. However, caffeine overdose can lead to acute intoxication, posing a clinical problem. Hyperthermia and hyperactivity are associated issues with acute caffeine intoxication; however, no definitive treatment exists. This study aimed to assess the ability of risperidone to attenuate caffeine-induced hyperthermia and hyperactivity while elucidating the unknown mechanisms of caffeine intoxication. The rats received intraperitoneal injections of saline, risperidone (0.25 mg/kg, 0.5 mg/kg), WAY-100635, ketanserin, haloperidol, sulpiride, or SCH 23390, 5 min after the administration of caffeine (25 mg/kg). Subcutaneous temperature and activity counts were measured using nano tag ® for up to 90 min. In vivo microdialysis was used to determine the effect of risperidone on caffeine-induced elevation of dopamine (DA), serotonin (5-HT), and noradrenaline (NA) concentrations in the anterior hypothalamus. Rats were injected with caffeine (25 mg/kg), followed by saline or risperidone (0.5 mg/kg) 5 min later. The levels of DA, 5-HT, and noradrenaline were measured every 15 min for up to 90 min after caffeine administration. Risperidone and 5-HT2A receptor antagonist ketanserin attenuated caffeine-induced hyperthermia and hyperactivity. Haloperidol and dopamine D1 antagonist SCH-23390 exacerbated hyperthermia without any effect on the hyperactivity. In the microdialysis study, risperidone treatment further attenuated caffeine-induced 5-HT elevation, but not DA and NA. Our results indicate that risperidone attenuates caffeine-induced hyperthermia and hyperactivity by blocking 5-HT2A receptor activity and may be potentially useful for treating caffeine intoxication.

Syndrome of inappropriate antidiuretic hormone secretion induced by suvorexant: a case report.

NONE: Syndrome of inappropriate antidiuretic hormone release (SIADH) can sometimes be caused by an adverse effect of certain psychotropic drugs. However, suvorexant has never been reported to cause SIADH. A 77-year-old man with type 2 diabetes was admitted to the Jichi Medical University Hospital for the treatment of major depression. During the treatment, he was prescribed suvorexant for insomnia. Twelve days after the initiation of suvorexant, he developed hyponatremia, which met the diagnostic criteria of SIADH. We suspected the hyponatremia to be an adverse drug effect of suvorexant because no other cause for SIADH was detected. Accordingly, suvorexant was discontinued 15 days after the onset of SIADH, and hyponatremia improved in 6 days. Although suvorexant has fewer adverse drug reactions and is considered relatively safe, clinicians should be aware of the possibility of SIADH induced by suvorexant.

Rapid upregulation of endothelial P-selectin expression via reactive oxygen species generation.

Endothelial cell ICAM-1 upregulation in response to TNF-alpha is mediated in part by reactive oxygen species (ROS) generated by the endothelial membrane-associated NADPH oxidase and occurs maximally after 4 h as the synthesis of new protein is required. However, thrombin-stimulated P-selectin upregulation is bimodal, the first peak occurring within minutes. We hypothesize that this early peak, which results from the release of preformed P-selectin from within Weibel-Palade bodies, is mediated in part by ROS generated from the endothelial membrane-associated xanthine oxidase. We found that this rapid expression of P-selectin on the surface of endothelial cells was accompanied by qualitatively parallel increases in ROS generation. Both P-selectin expression and ROS generation were inhibited, dose dependently, by the exogenous administration of disparate cell-permeable antioxidants and also by the inhibition of either of the known membrane-associated ROS-generating enzymes NADPH oxidase or xanthine oxidase. This rapid, posttranslational cell signaling response, mediated by ROS generated not only by the classical NADPH oxidase but also by xanthine oxidase, may well represent an important physiological trigger of the microvascular inflammatory response.

Solid-pseudopapillary tumor of the pancreatic head causing marked distal atrophy: a tumor originated posterior to the main pancreatic duct.

We report the case of a solid-pseudopapillary tumor (SPT) of the head of the pancreas causing occlusion of the main pancreatic duct (MPD) and marked pancreatic atrophy distal to the tumor disproportionate to the tumor size. A 15-yr-old girl was diagnosed with 5-cm solid-pseudopapillary tumor of the pancreatic head with marked distal pancreatic atrophy. Endoscopic retrograde cholangiopancreatography demonstrated obstruction of the MPD in the pancreatic head. We performed a duodenum-preserving pancreatic head resection to avoid postoperative exocrine and endocrine insufficiency. The surgical specimen showed the typical gross appearance of a SPT, with only a thin rim of pancreas anterior to the tumor. We believe that this presentation results when a tumor originates posterior to the MPD. Thus, whether or not pancreatic atrophy occurs depends strongly on the anterior/posterior relationship between the enlarging tumor and the MPD. The risk of SPT causing severe pancreatic atrophy should be kept in mind to avoid irreversible pancreatic insufficiency in young females.