Noribogaine (noribo) is the primary metabolite from ibogaine, an atypical psychedelic alkaloid isolated from the root bark of the African shrub Tabernanthe iboga. The main objective of this study was to test the hypothesis that molecular, electrophysiological, and behavioral responses of noribo are mediated by the 5-HT_2A receptor (5-HT_2AR) in mice. In that regard, we used male and female, 5-HT_2AR knockout (KO) and wild type (WT) mice injected with a single noribo dose (10 or 40 mg/kg; i.p.). After 30 min., locomotor activity was recorded followed by mRNA measurements by qPCR (immediate early genes; IEG, glutamate receptors, and 5-HT_2AR levels) and electrophysiology recordings of layer V pyramidal neurons from the medial prefrontal cortex. Noribo 40 decreased locomotion in male, but not female WT. Sex and genotype differences were observed for IEG and glutamate receptor expression. Expression of 5-HT_2AR mRNA increased in the mPFC of WT mice following Noribo 10 (males) or Noribo 40 (females). Patch-clamp recordings showed that Noribo 40 reduced the NMDA-mediated postsynaptic current density in mPFC pyramidal neurons only in male WT mice, but no effects were found for either KO males or females. Our results highlight that noribo produces sexually dimorphic effects while the genetic removal of 5HT_2AR blunted noribo-mediated responses to NMDA synaptic transmission.

Epilepsy is a neurological disease present in a wide range of mammals, including humans and domestic canines and felines. The most commonly used pharmacological treatments for canines are phenobarbital and potassium bromide (KBr). However, both of these medications are partially eliminated through the kidneys, which could potentially cause damage at this level. Current diagnostic methods for kidney damage typically identify issues only at advanced stages, highlighting the need for early detection techniques. Thus, this study aims to evaluate early renal alterations in canines diagnosed with idiopathic epilepsy and treated with phenobarbital and/or KBr, using specific biomarkers such as kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL), alongside non-specific biomarkers such as C-reactive protein (C-RP). Data from 39 canines treated at the Veterinary Hospital Centre (Udelar) and private clinics in Montevideo, Uruguay, were analysed. Subjects were categorised into two groups: a control group (healthy animals) and a group of subjects previously diagnosed with idiopathic epilepsy. The latter group was subdivided into three additional groups: one treated with phenobarbital, one treated with phenobarbital/KBr, and one treated with KBr alone. Laboratory results were evaluated for new biomarkers and conventional analytes. No alterations were found in laboratory tests for liver function, profiles, or urinalysis among the 30 canines subjected to the different treatments. Regarding specific biomarkers, no statistically significant differences (p > 0.05) were observed among the groups. However, alterations in C-RP were found in the group treated only with KBr. Under the conditions of the trial, no significant changes were detected in urinalysis or renal profiles associated with the administration of phenobarbital and/or potassium bromide in canines with idiopathic epilepsy.