AMN 082 dihydrochloride

AMN 082 dihydrochloride is a selective mGlu₇ positive allosteric agonist. It is orally active and blood-brain barrier permeable.

AMN 082 binds at the mGlu₇ allosteric site and at ≤10 μM fails to show appreciable activating or inhibitory effects at other mGluR subtypes and selected iGluRs.

Uses

AMN 082 effects may differ depending on brain region. For example, AMN082 decreases GABA and increases glutamate levels in the nucleus accumbens and amygdala and decreases glutamate and GABA release in the periaqueductal gray (PAG).

It potently inhibits accumulation of cAMP and stimulates GTPγS binding (EC₅₀ = 64 - 290 nM) with agonist efficacies comparable with those of L-AP4. AMN082 also increase splasma corticosterone and ACTH levels.

AMN082 reduces fear acquisition and LTP in the amygdala but improves fear extinction. AMN 082 also produces anxiogenic- and anxiolytic-like effects, can facilitate nociception, shows anti-depressant-like activity, reduces ethanol and cocaine intake and facilitates extinction of aversive memories.

In vitro use – guidelines

Non-specific actions may be observed at concentrations of 3-10 µM and above.

Therefore, for researchers wishing to investigate selective mGlu₇ actions, it is recommended that this product is not used above concentrations of 1μM.

In vivo use – guidelines

Guidelines for maximally tolerated doses in vivo are: 6 mg/kg p.o. in mice and 20 mg/kg p.o. in rats

• Those doses result in mGlu₇-dependent physiological effects, e.g. modulation of stress-hormones.
• However, non-selective effects have been observed at higher doses (2-3 times higher than those stated above).
• Examples of such non-selective effects include head twists and tremor observed in mGlu₇+/+ (wild-types) and mGlu₇-/- mice (knock-outs).
• The product can be orally administered (p.o.) in a methylcellulose suspension. For further details contact Dr. John F. Cryan at University College Cork. There is currently no data available on maximally tolerated doses for i.v., i.c.v., or i.p. routes of administration.

Use of knock-outs for validation of data

• Dr. Peter J. Flor and his colleagues recommend that the physiological and pharmacological effects of AMN082 should ideally be confirmed by evaluation in mGlu₇+/+ (wild-types) versus mGlu₇-/- mice (KO).
• Effects of AMN082 that are seen in mGlu₇+/+ (wild-types) but not in mGlu₇-/- mice (KO) are most likely mGlu₇+/+ -mediated.
• For details on obtaining mGlu₇+/+ (wild-types) and mGlu₇-/- mice (KO) please contact Dr. Peter J. Flor or Dr. Herman van der Putten.

• If possible, make up solutions and use immediately.
• If storage of solutions is required, you should aliquot out the solution into tightly sealed vials and store at -20°C and store these for up to one month.
• Allow the product to equilibrate to RT for at least one hour before opening and using.
• Always check that your product is completely dissolved before use. The solution should be precipitate-free, clear and colourless.
• Once removed from -20°C, and brought to room temperature, it is recommended that the solution is used immediately.