ZCZ011 is a positive allosteric modulator of the cannabinoid CB1 receptor. ZCZ011 is brain penetrant, increased the potency of orthosteric agonists in mouse behavioral assays indicative of cannabimimetic activity, including antinociception, hypothermia, c
Arachidonoyl 2-chloroethylamide (ACEA) is a potent and selective cannabinoid (CB) receptor 1 agonist with Ki values of 1.4 and >2,000 nM for CB1 and CB2 receptors, respectively. In whole animal experiments, ACEA induces hypothermia in mice with the same efficacy as arachidonoyl ethanolamide , in spite of its higher affinity for the CB1 receptor. These data have been interpreted to indicate that ACEA may be a substrate for fatty acid amide hydrolase (FAAH), and thus only transiently available in whole animal experiments.
SR 142948A is a non-peptide antagonist of neurotensin receptor. SR 142948A affects the expression of c-Fos and has properties of antipsychotic agent. SR 142948A blocks hypothermia and analgesia induced by neurotensin. It blocks the increase in the concent
2-Aminotetralin acts as a neuromodulatory agent by inhibiting serotonin (5-HT) and norepinephrine reuptake in the rat brain at a dose of 39.4 mg kg. It triggers hypothermia in rats through intracisternal or intraperitoneal injection, while the implantation of crystals in the hypothalamus' medial preoptic area leads to hyperthermia. Additionally, it mimics (+)-amphetamine in a two-lever drug discrimination test among rats in a dose-dependent manner.
(±)-N-desmethyl Venlafaxine, a minor active metabolite of venlafaxine, serves as a selective norepinephrine and serotonin reuptake inhibitor (SNRI). Generated through the metabolization by the cytochrome P450 (CYP) isoform CYP3A4, it exhibits reuptake inhibition of norepinephrine and serotonin in rat synaptosome preparations, demonstrated by IC50 values of 4.7 and 1.6 µM, respectively. Clinically, it has been shown to counteract reserpine-induced hypothermia in mice, displaying efficacy at a minimum effective dose (MED) of 10 mg kg.