Uses
MPEP is a potent and highly selective non-competitive mGlu5a receptor antagonist (1,2). It is also a positive allosteric modulator at mGlu4 receptors.MPEP exhibits anxiolytic and antidepressant properties that may be applicable for treating schizophrenia (3).
Definition
ChEBI: 2-methyl-6-(phenylethynyl)pyridine is a methylpyridine that coinsists of 2-methylp[yridine bearing an additional phenylethynyl group at position 6. Potent and highly selective non-competitive antagonist at the mGlu5 receptor subtype (IC50 = 36 nM) and a positive allosteric modulator at mGlu4 receptors. Centrally active following systemic administration in vivo. Reverses mechanical hyperalgesia in the inflamed rat hind paw. It has a role as a metabotropic glutamate receptor antagonist and an anxiolytic drug. It is a member of methylpyridines and an acetylenic compound. It is a conjugate base of a 2-methyl-6-(phenylethynyl)pyridinium(1+). It derives from a hydride of an acetylene.
Biological Activity
Potent and highly selective non-competitive antagonist at the mGlu 5 receptor subtype (IC 50 = 36 nM) and a positive allosteric modulator at mGlu 4 receptors. Centrally active following systemic administration in vivo . Reverses mechanical hyperalgesia in the inflamed rat hind paw. Also available as part of the Group I mGlu Receptor Tocriset™ .
in vivo
MPEP (1-30 mg/kg) induces anxiolytic-like effects in the conflict drinking test and the elevated plus-maze test in rats as well as in the four-plate test in mice[2].
MPEP (1-20 mg/kg) does shorten the immobility time in a tail suspension test in mice, however it is inactive in the behavioural despair test in rats[2].
MPEP (30 mg/kg i.p.) slightly but significantly increases (by 39%) the number of punished crossings in the four-plate test, lower doses of the compound (3 and 10 mg/kg) does not affect the number of punished crossings in that test (F (3,36)=3.240, P<0.05)[2].
MPEP (1, 10 and 20 mg/kg) significantly (by 55% after the highest dose), (F(3,28)=15.47, P<0.001) decreases the immobility time of mice in the tail suspension test. Its efficacy is similar to that of imipramine (20 mg/kg), used as the positive standard[2].
| Animal Model: | Male Wistar rats (200 ± 250 g)[2].
|
| Dosage: | IP or PO. |
| Administration: | 0.3, 1 and 10 mg/kg, i.p. (Conflict drinking test). |
| Result: | At a dose of 0.3 mg/kg was not ffective, at doses of 1 and 10 mg/kg i.p. significantly (F (3,30)=11.193, P<0.001), increased the number of shocks (by 330 and 507%, respectively) accepted during the experimental session in the Vogel test. |
| Animal Model: | Male Wistar rats (200 ± 250 g)[2].
|
| Dosage: | IP or PO. |
| Administration: | 1, 3 and 10 mg/kg, i.p. or 10 and 30 mg/kg, p.o.(Elevated plus-maze test). |
| Result: | Administered at a dose of 1 mg kg71 i.p. did not change the entries into and time spent in the open arms. At doses of 3 and 10 mg/kg i.p. significantly (F (3,24)=22.978, P<0.001) dose-dependently increased the time spent in the open arms (up to 45 and 74%, respectively), and the percentage of entries into the open arms (up to 48 and 68%, respectively, F(3,24)=5.678, P<.01). At doses of 3 and 10 mg/kg i.p. significantly increased (by 64%) the total number of entries and reduced (by about 25%) the total time
spent (data not shown) in the arms (either type).
At the dose of 30 mg/kg (po, but not 10 mg/kg) significantly (up to 64%, F (2,16)=14.249, P<0.001) increased the percentage of the time spent in the open arms and the percentage of entries into the open arms (up to 63%, F (2,16)=7.295, P<0.01). MPEP given p.o. in both doses used did not change the total number of entries nor the total time spent in the arms (either type).
|
References
[1] gasparini f, lingenhöhl k, stoehr n, et al. 2-methyl-6-(phenylethynyl)-pyridine (mpep), a potent, selective and systemically active mglu5 receptor antagonist. neuropharmacology, 1999, 38(10): 1493-1503.
[2] tatarczyńska e, kłodzińska a, chojnacka-wójcik e, et al. potential anxiolytic-and antidepressant-like effects of mpep, a potent, selective and systemically active mglu5 receptor antagonist. british journal of pharmacology, 2001, 132(7): 1423-1430.
