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Chemical Compound Review

Phaclofen     [3-amino-2-(4-chlorophenyl) propyl]phosphon...

Synonyms: SureCN339995, P118_SIGMA, AG-K-92316, CHEMBL1255941, ACMC-20djlx, ...
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Disease relevance of Phaclofen

  • METHODS: Effects of the GABA(B) receptor agonist ((+/-)-baclofen), antagonist (phaclofen), and their combination were tested against clonic seizures induced by cocaine (75 mg/kg) [1].
  • RESULTS: Spinal administration of the GABAA receptor antagonist bicuculline or the GABAB receptor antagonist phaclofen produced tactile allodynia and thermal hyperalgesia in normal rats [2].
  • Similarly, phaclofen (500 microM), as well as pertussis toxin (140 ng/ml, overnight incubation) did not modify these effects [3].
  • Moreover, bilateral injection of the GABA(B) antagonist, phaclofen, into the LA increased both EMG responses to combined TN and MGN stimulation across various ISIs, and EMG responses to combined TN and AAC stimulation at short ISIs [4].
  • Similarly, phaclofen failed to alter Ve and Vo(2 peak) in obese rats, although it did significantly increase f after 5-20 min of hypoxia [5].

Psychiatry related information on Phaclofen


High impact information on Phaclofen

  • The ionic basis for this response remains unknown, though it is not, unlike the response to GABAA receptor activation, mediated by an increase in conductance to Cl-. The effects of GABAB receptor antagonism with phaclofen are mimicked by pretreatment of the spinal cord with PTX [7].
  • The GABAB receptor antagonist phaclofen prevented, with identical affinities, the effects of (-)-baclofen on SRIF (pKb = 4.9) and CCK (pKb = 4.8) release [8].
  • The inhibition of endozepine secretion evoked by GABA and baclofen (10(-5) M each) was totally abrogated by the specific GABA(B) receptor antagonist phaclofen (10(-4) M) [9].
  • However, phaclofen and structurally similar derivatives 3-5 did not cross the blood-brain barrier and hence were inactive in vivo as central nervous system agents [10].
  • When GABAA (bicuculline) and GABAB (phaclofen) antagonists were simultaneously bath applied to the lumbar spinal cord, however, locomotor-like activity was induced [11].

Chemical compound and disease context of Phaclofen


Biological context of Phaclofen


Anatomical context of Phaclofen

  • Bicuculline (100 microM), picrotoxin (50 microM) and phaclofen (300 microM) alone had no effect on [3H]acetylcholine release during splanchnic nerve stimulation [21].
  • In animals (n = 5) treated with phaclofen, 18 of 251 sites (7.2%) responded to hindlimb stimulation before treatment and 64 of these sites (25.5%) responded to such stimulation during application (P < 0.05) [22].
  • 2. After intracortical microstimulation (0.5-6 microA), fast and slow inhibitory postsynaptic potentials (IPSPs) were produced in layers II-VI pyramidal cells and selectively reduced with bicuculline methiodide and phaclofen, respectively [23].
  • Moreover, phaclofen (GABA(B) receptor antagonist) treated SR gerbil showed reduction in calbindin D-28K immunoreactivity, not parvalbumin immunoreactivity, in the hippocampus [24].
  • To specifically test the role of GABA(A) versus GABA(B) receptors in the inhibition of hindlimb input to the SI stump representation in rats that sustained neonatal forelimb removal, either bicuculline or phaclofen alone was applied to SI in nine neonatally manipulated animals [22].

Associations of Phaclofen with other chemical compounds


Gene context of Phaclofen

  • This effect was stereospecific and blocked by GABAB receptor antagonists like CGP 35 348 (3-aminopropyl-diethoxymethyl-phosphonic acid) and phaclofen [30].
  • Bicuculline or phaclofen, given alone, did not alter the plasma extravasation response after either electrical stimulation or SP administration [31].
  • 3. The late IPSP, in contrast, had an average reversal potential of -95 mV, was associated with a mean 12-nS increase in membrane conductance, was reduced by the GABAB antagonist phaclofen, and was mimicked by the GABAB agonist baclofen [32].
  • The GABAA antagonist, bicuculline, inhibited muscimol's effect, whereas the GABAB antagonist, phaclofen, did not [33].
  • In the phaclofen-treated SS gerbils, VGAT expression was dramatically elevated, compared to SS gerbil controls [34].

Analytical, diagnostic and therapeutic context of Phaclofen

  • 3. Bicuculline (20-100 microM) and picrotoxin (50 microM) alone reduced [3H]acetylcholine release during electrical stimulation of the lumbar colonic nerves whereas phaclofen (300 microM) had no effect [21].
  • Intracortical perfusion of the GABA(B) receptor antagonists, CGP 35348 and phaclofen as well as the GHB receptor antagonist, NCS 382 attenuated GHB-mediated changes in the basal and K+-evoked release of GABA [35].
  • In contrast, the inhibition produced by PAG stimulation in most of the cells examined was not significantly antagonized by the GABAB antagonists phaclofen or 3-amino-propyl(diethoxymethyl)phophinic acid (CGP35348) administered into the spinal dorsal horn by microdialysis [36].
  • Microinjections of the postsynaptic GABAB receptor antagonist phaclofen, which blocks the actions of GABA at postsynaptic but not at presynaptic GABAB receptor sites, did not block the phase-shifting actions of either muscimol or baclofen [12].


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  12. Bicuculline and picrotoxin block phase advances induced by GABA agonists in the circadian rhythm of locomotor activity in the golden hamster by a phaclofen-insensitive mechanism. Smith, R.D., Turek, F.W., Slater, N.T. Brain Res. (1990) [Pubmed]
  13. Spinal and supraspinal antinociceptive action of dipyrone in formalin, capsaicin and glutamate tests. Study of the mechanism of action. Beirith, A., Santos, A.R., Rodrigues, A.L., Creczynski-Pasa, T.B., Calixto, J.B. Eur. J. Pharmacol. (1998) [Pubmed]
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  20. Intrathecal GABAB antagonists attenuate the antinociception produced by microinjection of L-glutamate into the ventromedial medulla of the rat. McGowan, M.K., Hammond, D.L. Brain Res. (1993) [Pubmed]
  21. Enteric GABA-containing nerves projecting to the guinea-pig inferior mesenteric ganglion modulate acetylcholine release. Parkman, H.P., Stapelfeldt, W.H., Williams, C.L., Lennon, V.A., Szurszewski, J.H. J. Physiol. (Lond.) (1993) [Pubmed]
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  31. Peripheral GABAA receptor-mediated effects of sodium valproate on dural plasma protein extravasation to substance P and trigeminal stimulation. Lee, W.S., Limmroth, V., Ayata, C., Cutrer, F.M., Waeber, C., Yu, X., Moskowitz, M.A. Br. J. Pharmacol. (1995) [Pubmed]
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