| Description |
Lu AF21934 is a selective and brain-penetrant mGlu4 receptor positive allosteric modulator with an IC50 of 500 nM for human mGlu4.
|
| Related Catalog |
|
| Target |
IC50: 500 nM (hmGlu4)[1]
|
| In Vivo |
Lu AF21934 treatment shows a dose-dependent anxiolytic-like effect in the stress-induced hyperthermia, four-plate, and marble-burying tests. The anti-hyperthermic effect of Lu AF21934 (5 mg/kg) in the SIH test is inhibited by the benzodiazepine receptor antagonist flumazenil (10 mg/kg) and is not serotonin dependent. Lu AF21934 does not produce antidepressant-like effects in the tail suspension test in mice; however, it decreases the basal locomotor activity of mice that are not habituated to activity cages[1]. Lu AF21934 (0.5-5 mg/kg sc) does not influence tremor but at doses of 0.5 and 2.5 mg/kg reverses harmaline-induced hyperactivity. Lu AF21934 at a dose of 2.5 mg/kg potentiates the inhibitory influence of harmaline on the exploratory activity and AP1 during the first 30 min of the measurement and counteracts the harmaline-increased basic activity during the period of 30-90 min[2]. Lu AF21934 (0.1-5 mg/kg) dose-dependently inhibits hyperactivity induced by MK-801 or amphetamine. It also antagonizes head twitches and increases frequency of spontaneous excitatory postsynaptic currents in brain slices, induced by DOI[3].
|
| Animal Admin |
Rats: Lu AF21934 is dispersed in 20% (2-hydropropyl)-b-cyclodextrin and are administered subcutaneously (s.c.) 60 min before the test. Lu AF21934 (2, 5, 10 and 15 mg/kg, s.c.) and diazepam (5 mg/kg, i.p.) are administered acutely 1 h before the Vogel’s conflict test. The effects of each drug in all experiments are measured in groups of 8-10 animals[1]. Mice: Lu AF21934 is dispersed in 20% (2-hydropropyl)-b-cyclodextrin and are administered subcutaneously (s.c.) 60 min before the test. Mice are gently placed into the box and allowed to explore for 15 s. Then, each time a mouse passed from one plate to another, the experimenter electrifies the whole floor thus evoking a visible flight reaction of the animal. If the animal continues running, no new shock is delivered for the following 3 s[1].
|
| References |
[1]. Sławińska A, et al. Anxiolytic- but not antidepressant-like activity of Lu AF21934, a novel, selective positive allosteric modulator of the mGlu₄ receptor. Neuropharmacology. 2013 Mar;66:225-35. [2]. Ossowska K, et al. Lu AF21934, a positive allosteric modulator of mGlu4 receptors, reduces the harmaline-induced hyperactivity but not tremor in rats. Neuropharmacology. 2014 Aug;83:28-35. [3]. Sławińska A, et al. The antipsychotic-like effects of positive allosteric modulators of metabotropic glutamate mGlu4 receptors in rodents. Br J Pharmacol. 2013 Aug;169(8):1824-39.
|
