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PubMed2002

Effect of cannabinoids on synaptic transmission in the rat hippocampal slice is temperature-dependent.

We have previously reported that the synthetic cannabinoid R-(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazin-yl]-(1-naphthalenyl)methanone mesylate (WIN55,212-2) causes a selective inhibition of paired pulse depression of population spikes recorded from the CA1 region of rat hippocampal slices maintained at 28-30 degrees C. We now show that this effect is highly temperature-dependent and that WIN55,212-2 actually increases paired pulse depression of population spikes recorded from slices maintained at 35 degrees C. This temperature dependence was found to correlate with the effects of the known gamma-amino butyric acid (GABA)-uptake inhibitors, nipecotic acid and guvacine, which were without effect at 28-30 degrees C, but increased paired pulse depression at 35 degrees C. The results show that the effects of cannabinoids on synaptic transmission in the hippocampal slice are highly temperature-dependent and it is suggested that this is due to the presence of increased GABA uptake at higher temperatures.

Animals↗
PubMed1998

Postsynaptic integration of cholinergic and dopaminergic signals on medium-sized GABAergic projection neurons in the neostriatum.

The effects of cholinergic drugs and the interaction between cholinergic and dopaminergic compounds were studied on electrically evoked [3H]gamma-aminobutyric acid (GABA) overflow in slices of the rat neostriatum. Slices were prepared and loaded with [3H]GABA in the presence of beta-alanine and then superfused with Krebs-bicarbonate buffer containing aminooxyacetic acid and nipecotic acid to inhibit GABA uptake and metabolism, respectively. The nonselective muscarinic agonist oxotremorine (0.1-10 microM) increased the release of [3H]GABA and the selective M1 receptor agonist McN-A-343 (0.1-10 microM) exerted similar effect. The stimulatory effect of oxotremorine (10 microM) on [3H][GABA overflow was antagonized by the nonselective muscarinic antagonist atropine (1 microM) and the selective M1 receptor antagonist pirenzepine (0.1-1.0 microM). The M2 receptor antagonist methoctramine (1.0 microM) did not alter the stimulatory effect of oxotremorine. Of the muscarinic receptor antagonists atropine, pirenzepine, and methoctramine (1.0 microM) failed to affect [3H]GABA overflow. The M3 receptor antagonist p-F-HHSiD (1 microM) increased [3H]GABA overflow and p-F-HHSiD and oxotremorine were found to be additive in increasing this effect. The D2 dopamine receptor antagonist sulpiride (10 microM) increased the electrical stimulation-induced [3H]GABA overflow, and this stimulation was counteracted by concomitant administration of atropine (1 microM). McN-A-343 and sulpiride also increased the KCl-induced [3H]GABA overflow from superfused neostriatal slices and tetrodotoxin (1 microM) did not affect these stimulations. These data indicate that the release of GABA in the neostriatum is under the control of M1 stimulatory and M3 inhibitory muscarinic receptors. Dopamine, which exerts inhibition on GABA release via D2 receptors, may counteract the M1 facilitation, and M1 and D2 receptors involved in the cholinergic-dopaminergic interaction may be located postsynaptically on medium-sized spiny GABAergic projection neurons.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗
PubMed1998

Functional significance of the "signature cysteine" in helix 8 of the Escherichia coli 4-aminobutyrate transporter from the amine-polyamine-choline superfamily. Restoration of Cys-300 to the Cys-less Gabp.

gab permease (GabP) is the exclusive mediator of 4-aminobutyrate (GABA) transport across the Escherichia coli plasma membrane. Helix 8 and a portion of the adjoining cytoplasmic region (loop 8-9) constitute the GabP "consensus amphipathic region" (CAR), a potential channel-forming domain that is found to be evolutionarily conserved within the APC (amine-polyamine-choline) transporter superfamily. Upon the polar surface of the CAR, all known gab permeases display a "signature cysteine" not found in other members of the APC superfamily, suggesting that discrete features within the CAR might play a role in imparting specificity (kcat/Km) to the translocation reaction. Here we show that among the five cysteine residues in the E. coli GabP, only Cys-300, the signature cysteine, can restore wild type properties to the Cys-less GabP mutant. We conclude (i) from partial reaction studies (equilibrium exchange, counterflow) that rapid translocation of the GABA binding site from one side of the membrane to the other is greatly facilitated by Cys-300 and (ii) from pharmacological studies that loss of Cys-300 has little effect on the affinity that GabP exhibits for a structurally diverse array (kojic amine, 5-aminovaleric acid, GABA, nipecotic acid, and cis-4-aminocrotonic acid) of competitive ligands. These results raise the possibility that other GABA transporters might rely analogously upon conserved cysteine residues positioned within the amphipathic helix 8 and loop 8-9 regions.

Amino Acid Sequence↗
PubMed1988

Loss of cortical GABA uptake sites in Alzheimer's disease.

[3H]Nipecotic acid bound to membranes of human brain in a saturable, reversible manner which was totally dependent on the presence of sodium ions. The potencies of compounds in inhibiting the specific binding of [3H]nipecotic acid were closely correlated with their potencies in inhibiting the neuronal uptake of [3H]GABA. Compounds selective for GABA receptors were inactive. [3H]Nipecotic acid appears to label neuronal high affinity GABA uptake sites. The binding of [3H]nipecotic acid was substantially reduced in the temporal cortex of brains from subjects with Alzheimer-type dementia, but not in other brain regions. It is concluded that some loss of GABA terminals occurs in this disease.

Aged↗
PubMed2000

GABA uptake inhibitors. Design, molecular pharmacology and therapeutic aspects.

In the mid seventies a drug design programme using the Amanita muscaria constituent muscimol (7) as a lead structure, led to the design of guvacine (23) and (R)-nipecotic acid (24) as specific GABA uptake inhibitors and the isomeric compounds isoguvacine (10) and isonipecotic acid (11) as specific GABAA receptor agonists. The availability of these compounds made it possible to study the pharmacology of the GABA uptake systems and the GABAA receptors separately. Based on extensive cellular and molecular pharmacological studies using 23, 24, and a number of mono- and bicyclic analogues, it has been demonstrated that neuronal and glial GABA transport mechanisms have dissimilar substrate specificities. With GABA transport mechanisms as pharmacological targets, strategies for pharmacological interventions with the purpose of stimulating GABA neurotransmission seem to be (1) effective blockade of neuronal as well as glial GABA uptake in order to enhance the inhibitory effects of synaptically released GABA, or (2) selective blockade of glial GABA uptake in order to increase the amount of GABA taken up into, and subsequently released from, nerve terminals. The bicyclic compound (R)-N-Me-exo-THPO (17) has recently been reported as the most selective glial GABA uptake inhibitor so far known and may be a useful tool for further elucidation of the pharmacology of GABA transporters. In recent years, a variety of lipophilic analogues of the amino acids 23 and 24 have been developed, and one of these compounds, tiagabine (49) containing (R)-nipecotic acid (24) as the GABA transport carrier-recognizing structure element, is now marketed as an antiepileptic agent.

Animals↗
PubMed1989

Cardiovascular responses elicited by gamma-aminobutyric acid in the nucleus tractus solitarius: evidence for action at the GABAB receptor.

Previous studies in this laboratory have shown that GABAergic neurotransmission in the nucleus tractus solitarius contributes to the maintenance of blood pressure. Increasing the synaptic action of GABA in the nucleus tractus solitarius by injection of the blocker of the uptake of GABA, nipecotic acid elevated blood pressure. The current studies examined the subtype of GABA receptor involved in mediating this response. Bilateral injections of (-)baclofen into the nucleus tractus solitarius (1-100 pmol in 100 nl) of chloralose-anesthetized, paralyzed, ventilated Sprague-Dawley rats increased blood pressure without significantly altering heart rate. This pressor response was neither attenuated nor blocked by the selective GABAA receptor antagonist bicuculline. Similarly, the pressor response elicited by the injection of nipecotic acid into the nucleus tractus solitarius was totally unaffected by the GABAA receptor blockade with bicuculline. Since nipecotic acid acts by potentiating the action of synaptic GABA, and the GABA present presumably can interact with both GABAA and GABAB receptors, the observation that bicuculline did not block or attenuate the pressor response to nipecotic acid suggests that the pressor response to the enhanced synaptic action of GABA in the nucleus tractus solitarius can be produced independently of the involvement of GABAA receptors, and presumably is mediated through an action on GABAB receptors.

Animals↗
PubMed1985

GABAergic inhibition of hypertonic saline-induced vasopressin-dependent hypertension.

Previous studies have shown that hypotension produced by drugs facilitating gamma-aminobutyric acid (GABA) transmission was caused by a decrease in sympathetic nervous system outflow. We attempted to determine if GABA agonists and GABA uptake inhibitors could also lower arterial pressure that was elevated by increasing the secretion of endogenous vasopressin. GABA and nipecotic acid, an uptake inhibitor of GABA, were administered intraventricularly to determine the cardiovascular effects of these agents in nephrectomized rats made acutely hypertensive with hypertonic saline. A 2-hr i.v. infusion of hypertonic saline (3.0 mEq/ml) increased arterial pressure from 119 +/- 2 to 157 +/- 2 mm Hg. Intraventricular administration of artificial cerebrospinal fluid, 100 micrograms of GABA and 175 micrograms of nipecotic acid produced a peak decrease in blood pressure of 0 +/- 0, 30 +/- 4 and 22 +/- 3 mm Hg, respectively. In nephrectomized rats receiving an equal volume of isotonic saline (0.15 mEq/ml), infused i.v. arterial pressure did not change. In these animals, central infusions of artificial cerebrospinal fluid, 100 micrograms of GABA and 175 micrograms of nipecotic acid decreased blood pressure only 1 +/- 1, 13 +/- 2 and 8 +/- 3 mm Hg, respectively. Further experiments utilizing nephrectomized rats infused with hypertonic saline were designed to determine the mechanism for the augmented depressor response produced by these agents. Elimination of the contribution of vasopressin to arterial pressure with a vascular vasopressin antagonist reduced the depressor responses produced by 100 micrograms of GABA and 175 micrograms of nipecotic acid to 10 +/- 3 and 8 +/- 3 mm Hg, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminobutyrates↗
PubMed1986

Gamma-aminobutyric acid and the high pressure neurological syndrome.

Sodium valproate, nipecotic acid, diaminobutyric acid (DABA) and beta-alanine are drugs which enhance transmission mediated by gamma-aminobutyric acid (GABA) by a variety of mechanisms. They were used to study the role of GABA in the high pressure neurological syndrome (HPNS) in the rat. Sodium valproate, nipecotic acid and DABA reduced the increase in slow waves seen in the electroencephalogram (EEG) of control rats at pressures above 10-20 ATA; however, only sodium valproate had a beneficial effect on the behavioural signs of the high pressure neurological syndrome (tremor, myoclonus and convulsions). Sodium valproate is also thought to decrease neurotransmission produced by excitatory amino acids; thus, these results suggest that GABA is not one of the major neurotransmitters involved in all aspects of the high pressure neurological syndrome and that changes in excitatory neurotransmission may affect the behavioural signs.

Alanine↗
PubMed1999

Endogenous GABA potentiates the potassium-induced release of dopamine in striatum of the freely moving rat: a microdialysis study.

Using microdialysis, a study was made of the effects of an increase of endogenous GABA on basal and potassium-stimulated release of dopamine in striatum of the awake rat. The dopamine metabolites DOPAC and HVA were also measured. Extracellular concentrations of GABA were increased by inhibiting its uptake with nipecotic acid. TTX (10 microM) reduced basal extracellular concentrations of dopamine, and dopamine metabolites, but not GABA. Nipecotic acid (200, 500, and 1000 microM) produced a dose-related increase in basal extracellular concentrations of GABA, but did not change basal extracellular concentrations of dopamine and dopamine metabolites. However, nipecotic acid significantly enhanced the dopamine release produced by perfusion of potassium (50 mM) and also enhanced the extracellular increase of GABA produced by high potassium. These results suggest that an increase of endogenous GABA is facilitating the stimulated release, but not the basal release, of dopamine in the striatum of the awake rat.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

GABA uptake inhibitors containing mono- and diarylmethoxyalkyl N-substituents.

Analogues of GABA and the GABA uptake inhibitors, nipecotic acid and guvacine, carrying N-(mono)- or N-(diarylmethoxy)alkyl substituents were synthesized and tested in vitro as inhibitors of synaptosomal GABA uptake and GABAA receptor binding. Whereas the N-(diphenylmethoxy)ethyl derivative GABA (compound 23) (see Figures 1 and Scheme 1 for structures) was only a moderately potent inhibitor of GABA uptake, corresponding derivatives of nipecotic acid and guvacine compounds 7e and 16, respectively) were potent inhibitors having IC50 values in the low micromolar range. In the case of 7e, (a) the (R)-isomer (10) was three times more potent than the (S)-isomer (13), (b) the bis-4-chlorophenyl analogue (compound 7g) was more potent than 7e, (c) the introduction of an additional methylene group into the linkage between the nipecotic acid and benzhydryl ether moiety (to give 7f) did not significantly affect in vitro biological activity, and (d) removal of one of the phenyl groups, or replacement of the benzhydryl ether group by the conformationally restrained fluorenyloxy group (to give 7i), resulted in substantial loss of activity. None of the compounds synthesized showed detectable affinity for GABAA receptor sites.

Anticonvulsants↗
PubMed1995

Identification and functional characterization of a dual GABA/taurine transporter in the bullfrog retinal pigment epithelium.

Intracellular microelectrodes, fluorescence imaging, and radiotracer flux techniques were used to investigate the physiological response of the retinal pigment epithelium (RPE) to the major retinal inhibitory neurotransmitter, gamma-aminobutyric acid (GABA). GABA is released tonically in the dark by amphibian horizontal cells, but is not taken up by the nearby Müller cells. Addition of GABA to the apical bath produced voltage responses in the bullfrog RPE that were not blocked nor mimicked by any of the major GABA-receptor antagonists or agonists. Nipecotic acid, a substrate for GABA transport, inhibited the voltage effects of GABA. GABA and nipecotic acid also inhibited the voltage effects of taurine, suggesting that the previously characterized beta-alanine sensitive taurine carrier also takes up GABA. The voltage responses of GABA, taurine, nipecotic acid, and beta-alanine all showed first-order saturable kinetics with the following Km's: GABA (Km = 160 microM), beta-alanine (Km = 250 microM), nipecotic acid (Km = 420 microM), and taurine (Km = 850 microM). This low affinity GABA transporter is dependent on external Na, partially dependent on external Cl, and is stimulated in low [K]o, which approximates subretinal space [K]o during light onset. Apical GABA also produced a significant conductance increase at the basolateral membrane. These GABA-induced conductance changes were blocked by basal Ba2+, suggesting that GABA decreased basolateral membrane K conductance. In addition, the apical membrane Na/K ATPase was stimulated in the presence of GABA. A model for the interaction between the GABA transporter, the Na/K ATPase, and the basolateral membrane K conductance accounts for the electrical effects of GABA. Net apical-to-basal flux of [3H]-GABA was also observed in radioactive flux experiments. The present study shows that a high capacity GABA uptake mechanism with unique pharmacological properties is located at the RPE apical membrane and could play an important role in the removal of GABA from the subretinal space (SRS). This transporter could also coordinate the activities of GABA and taurine in the SRS after transitions between light and dark.

Animals↗
PubMed1991

Calcium-independent gamma-aminobutyric acid release from growth cones: role of gamma-aminobutyric acid transport.

Neuronal growth cones isolated in bulk from neonatal rat forebrain have uptake and K(+)-stimulated release mechanisms for gamma-aminobutyric acid (GABA). Up to and including postnatal day 5, the K(+)-stimulated release of [3H]GABA and endogenous GABA is Ca2+ independent. At these ages, isolated growth cones neither contain synaptic vesicles nor stain for synaptic vesicle antigens. Here we examined the possibility that the release mechanism underlying Ca2(+)-independent GABA release from isolated growth cones is by reversal of the plasma membrane GABA transporter. The effects of two GABA transporter inhibitors, nipecotic acid and an analogue of nipecotic acid, SKF 89976-A, on K(+)-stimulated release of [3H]GABA from superfused growth cones were examined. Nipecotic acid both stimulated basal [3H]GABA release and enhanced K(+)-stimulated release of [3H]GABA, which indicates that this agent can stimulate GABA release and is, therefore, not a useful inhibitor with which to test the role of the GABA transporter in K(+)-stimulated GABA release from growth cones. In contrast, SKF 89976-A profoundly depressed both basal and K(+)-stimulated [3H]GABA release. This occurred at similar concentrations at which uptake was blocked. These observations provide evidence for a major role of the GABA transporter in GABA release from neuronal growth cones.

Animals↗
PubMed2005

Quinolinic acid toxicity on orexin neurons blocked by gamma aminobutyric acid type A receptor stimulation.

Selective degeneration of hypothalamic orexin neurons, a hallmark of pathology in narcolepsy patients, is in part reproduced in hypothalamic slice cultures by application of an endogenous excitotoxin quinolinic acid. Depolarized membrane potential may be responsible for the vulnerability of orexin neurons to excitotoxicity. We show that stimulation of gamma-aminobutyric acid type A receptors, which is known to hyperpolarize orexin neurons, by muscimol or isoguvacine potently inhibits quinolinic acid cytotoxicity on orexin neurons. In addition, the protective effect of gamma-aminobutyric acid and a gamma-aminobutyric acid uptake blocker nipecotic acid is abolished by a gamma-aminobutyric acid type A antagonist picrotoxin. Norepinephrine and serotonin do not provide a neuroprotective effect. Thus, GABAergic inhibitory control may be a decisive factor regulating survival of orexin neurons under excitotoxic insults.

Animals↗
PubMed1996

Anticonvulsant activity of novel derivatives of 2- and 3-piperidinecarboxylic acid in mice and rats.

The relative ability of derivatives of 2-piperidinecarboxylic acid (2-PC; pipecolic acid) and 3-piperidinecarboxylic acid (3-PC; nipecotic acid) to block maximal electroshock (MES)-induced seizures, elevate the threshold for electroshock-induced seizures and be neurotoxic in mice was investigated. Protective index (PI) values, based on the MES test and rotorod performance, ranged from 1.3 to 4.5 for 2-PC benzylamides and from < 1 to > 7.2 for 3-PC derivatives. PI values based on elevation of threshold for electroshock-induced seizures and rotorod performance ranged from > 1.6 to > 20 for both types of derivatives. Since preliminary data indicated that benzylamide derivatives of 2-PC displace [3H]1-[1-(2-thienyl)-cyclohexyl]piperidine (TCP) binding to the phencyclidine (PCP) site of the N-methyl-D-aspartate (NMDA) receptor in the micromolar range and such low affinity uncompetitive antagonists of the NMDA receptor-associated ionophore have been shown to be effective anticonvulsants with low neurological toxicity, the 2-PC derivatives were evaluated in rat brain homogenates for binding affinity to the PCP site. Although all compounds inhibited [3H]TCP binding, a clear correlation between pharmacological activity and binding affinity was not apparent. Select compounds demonstrated minimal ability to protect against pentylenetetrazol-, 4-aminopyridine- and NMDA-induced seizures in mice. Corneal and amygdala kindled rats exhibited different sensitivities to both valproic acid and the nonsubstituted 2-PC benzylamide, suggesting a difference in these two models. Enantiomers of the alpha-methyl substituted benzylamide of 2-PC showed some ability to reduce seizure severity in amygdala kindled rats.

4-Aminopyridine↗
PubMed1993

Non-synaptic modulation of dorsal column conduction by endogenous GABA in neonatal rat spinal cord.

GABAA receptor activation can modulate axonal conduction in the isolated dorsal column of the neonatal rat spinal cord in vitro. However, it is not known whether axonal conduction in the dorsal column can be modulated by endogenous GABA in the developing spinal cord. We consequently compared the effects of GABA, a GABAA agonist, and a GABA uptake inhibitor on axonal conduction in the dorsal column of hemisected neonatal (0- to 9-day-old) rat spinal cords in vitro. Extracellular compound action potentials evoked by supramaximal stimuli were recorded at two points with glass microelectrodes. GABA (10(-4) to 10(-3) M) reversibly decreased the compound action potential amplitude and the population conduction velocity. At 10(-4) M, compound action potential amplitudes fell by 45.0 +/- 6.5% of control while the conduction velocity slowed by 11.8 +/- 4.3% (n = 5). The GABAA receptor agonist, isoguvacine, mimicked the effects of GABA on the dorsal column compound action potential. In contrast, while GABA at 10(-5) M decreased the amplitude by 7.7 +/- 3.1%, it increased conduction velocity by 9.7 +/- 1.3% (n = 5). The GABA uptake inhibitor, nipecotic acid (10(-3) M), consistently decreased the compound action potential amplitude by 17.7 +/- 6.5% (n = 6) but the conduction velocity slowed in four out of six preparations. In two instances, nipecotic acid decreased the amplitude and increased the conduction velocity. The effects of nipecotic acid on the dorsal column compound action potential were blocked in the presence of the GABAA antagonist bicuculline.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1986

Prolongation of gamma-aminobutyric acid-mediated inhibitory postsynaptic potentials by 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridin-3-ol (THPO).

The effects of 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridin-3-ol (THPO), an inhibitor of gamma-aminobutyric acid (GABA) uptake, were examined in the rat hippocampal slice and compared to the actions of the potent GABA uptake inhibitor, cis-4-OH-nipecotic acid. THPO reversibly prolonged GABA-mediated inhibitory postsynaptic potentials (IPSPs) but did not prolong conductance changes evoked by iontophoresed GABA. In contrast, cis-4-OH-nipecotic acid prolonged responses to iontophoresed GABA but had little effect on IPSPs. THPO reduced the intensity of spontaneous epileptiform bursts observed in elevated (8.5 mM) potassium; this effect was absent after addition of 100 microM bicuculline. These results suggest that drugs similar to THPO may be useful for enhancing GABA-mediated inhibition, but that THPO acts by a mechanism distinct from that of the GABA uptake inhibitor, cis-4-OH-nipecotic acid.

Animals↗
PubMed2004

Design, synthesis and in vitro evaluation on HRPE cells of ascorbic and 6-bromoascorbic acid conjugates with neuroactive molecules.

Preliminary investigations allowed us to anticipate that conjugation of nipecotic acid with L-ascorbate (AA) gave a prodrug endowed with anticonvulsant activity in mice. In view of these results, and in order to get deepen insight into the molecular aspects at the base of the transport mechanism, a second generation of compounds, based on 6-bromo-6-deoxy-L-ascorbic acid (BrAA) as the carrier molecule was designed and synthesized. Effects of the chirality of the transported drug was also investigated on R- and S-nipecotic acid. Interaction and uptake modalities were evaluated in our in vitro model based on human retinal pigment epithelium cells (HRPE), which expresses the membrane L-ascorbic acid (AA) SVCT2 transporters. A remarkable increase on SVCT2 affinity was found going from AA to BrAA conjugates, that is, 11 (Ki=1187+/-78 microM) versus 19 (Ki=193+/-14 microM) and 12 (Ki=39.8+/-3.2 microM) versus 20, (Ki=7.4+/-0.8 microM). Taken together, these data are in agreement with our initial hypothesis on the possibility to achieve better affinities by conjugation with AA analogs, and also consent to hypothesize the presence of accessory interactions that may improve transporters recognition.

Animals↗
PubMed1988

Fast HPLC estimation of gamma-aminobutyric acid in microdialysis perfusates: effect of nipecotic and 3-mercaptopropionic acids.

A method for rapid, automated (less than 5 min), and sensitive (detection limit 50 fmol/10 microliter) determination of gamma-aminobutyric acid (GABA) is described. The method is based on precolumn derivatization with o-phthaldialdehyde/t-butylthiol reagent and separation by reverse-phase HPLC with electrochemical detection under isocratic conditions. A 100 X 4 mm Nucleosil 3 C18 column was used; the mobile phase consisted of 0.15 M sodium acetate, 1 mM EDTA (pH 5.4), and 50% acetonitrile; the flow rate was 0.8 ml/min. The potential of the glassy carbon working electrode was +0.75 V. The method allows for the monitoring of GABA levels in the extracellular fluid sampled by microdialysis as documented in the present study when 0.5 mM nipecotic acid is infused via the probe, or 3-mercaptopropionic acid is injected at a dose of 100 mg/kg i.p. There was a 15-fold increase of extracellular GABA after nipecotic acid, whereas in the second case the inhibition of GABA synthesis was followed by a 74% decrease of GABA as compared to basal levels.

3-Mercaptopropionic Acid↗