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PubMed1982

gamma-Aminobutyric acid (GABA) receptor stimulation. II. Specificity of progabide (SL 76002) and SL 75102 for the GABA receptor.

Progabide and its immediate metabolite SL 75102 displace [3H]gamma-aminobutyric acid (GABA), [3H]muscimol and [3H]isoguvacine from their binding sites to membranes prepared from rat brain or human cerebellum and increase (SL 75102) [3H]flunitrazepam binding to rat cerebral cortex membranes. In contrast, these compounds have very weak or no effects on alpha or beta noradrenergic, histamine, muscarinic cholinergic or glycine receptors or on the [3H]imipramine or [3H]kainate binding sites. Neither progabide nor SL 75102 inhibit GABA synthesis, metabolism or uptake. Also, the uptake of norepinephrine, serotonin and dopamine into synaptosomes of cerebral regions is not affected by progabide. [3H]GABA release from substantia nigra slices is decreased by SL 75102 and progabide, in agreement with the hypothesis of a GABAergic autoreceptor controlling GABA release from its nerve terminals. These data suggest a specific agonist action of progabide and SL 75102 on GABA receptors.

Animals↗

PubMed1982

Pyrrolines as prodrugs of gamma-aminobutyric acid analogues.

delta 1-Pyrroline, 5-methyl-delta 1-pyrroline, and 5,5-dimethyl-delta 1-pyrroline have been identified as substances metabolized to gamma-aminobutyric acid (GABA), 4-aminopentanoic acid (methylGABA), and 4-amino-4-methylpentanoic acid (dimethylGABA), respectively. An enzyme system residing in the soluble fraction of rabbit liver catalyzes the conversion of delta 1-pyrroline to GABA and its lactam, 2-pyrrolidinone. Acetaldehyde, allopurinol, and cyanide inhibited the reaction. Incubation of deuterium-labeled delta 1-pyrroline with mouse brain homogenates produced deuterated GABA. Mouse liver 10,000 g supernatant and mouse brain homogenates converted 5-methyl-delta 1-pyrroline to methylGABA, and 5,5-dimethyl-delta 1-pyrroline to dimethylGABA. Four hours after intraperitoneal injection of 5-methyl-delta 1-pyrroline (200 mg/kg), methylGABA was detected in mouse brain (0.27 mumol/g). DimethylGABA (1.21 mumol/g) was determined in mouse brain 30 min after intraperitoneal administration of 5,5-dimethyl-delta 1-pyrroline (200 mg/kg). Neither methylGABA nor dimethylGABA penetrated into the central nervous system when administered in the periphery. The present studies suggest that pyrrolines may represent a chemical class of brain-penetrating precursors of pharmacologically active analogues of GABA.

Animals↗

PubMed1976

The effect on cortical mirror foci produced by ouabain of gamma-aminobutyric acid, dopamine and haloperidol injected into the rabbit caudate nucleus.

Epileptiform activity is inhibited by injection of dopamine, and potentiated by injections of haloperidol into the caudate nucleus. gamma-Aminobutyric acid (GABA) initially potentiates, and shortly after that inhibits the epileptoform activity in the cortex. The authors discuss a possibility of combined treatment of seizure states with dopamine-mimetic and GABA-mimetic agents.

Aminobutyrates↗

PubMed1995

Dual role of K+ and Na+ on the transport of [3H]-gamma-aminobutyric acid by synaptic plasma membrane vesicles.

The influence of the monovalent cations (Na+ and K+) and of the electrical gradient on the high-affinity [3H]-gamma-aminobutyric acid ([3H]GABA) transport was investigated in synaptic plasma membrane (SPM) vesicles isolated from sheep brain cortex. This process specifically requires internal K+, since when it is replaced by Li+, the delta psi remains of the same order of magnitude, but no uptake of [3H]GABA occurs. The influence of the external Na+ concentration on the rate of [3H]GABA uptake suggests that this mechanism exhibits two components, whose characteristics are determined by the delta psi. Depolarization reduces the Jmax of [3H]GABA influx and enhances the binding of Na+ associated to [3H]GABA transport. Nevertheless, depolarization does not affect the K0.5 of binding sites for Na+ and the stoichiometry of translocation. These results suggest that intravesicular K+ and external Na+ have a dual role on the mechanism of [3H]GABA uptake: K+ acts directly on the carrier and determines the membrane polarization; Na+ is cotransported with GABA and, according to the polarization state of the membrane, it modulates the operation of the carrier in its inward GABA translocation.

Animals↗

PubMed1996

5-HT2A receptor antagonists inhibit potassium-stimulated gamma-aminobutyric acid release in rat frontal cortex.

Several drugs selective for the serotonin 5-HT2A receptor were tested for their effects on spontaneous and K(+)-evoked [3H] gamma-aminobutyric acid (GABA) release from slices of rat frontal cortex. Under K+ stimulation, the antagonists ketanserin, spiperone, R-(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenethyl)]- 4-piperidinemethanol (MDL 100,907) and ritanserin inhibited GABA release by 12-31%. Rats were treated with the serotonin-depleting agent para-chlorophenylalanine and with the serotonergic neurotoxin para-chloroamphetamine. In para-chlorophenylalanine-treated animals, stimulated GABA release in the presence of ketanserin remained depressed. In animals treated with both para-chlorophenylalanine and para-chloroamphetamine, ketanserin or the hallucinogenic agonist (2,5-dimethoxy-4-iodophenyl)-2-aminoethane (2C-I) each appeared to decrease stimulated GABA release but this was not significant. However, when ketanserin and 2C-I were both present in the superfusion buffer an additive inhibitory effect was observed, and GABA release was decreased 30%. These results suggest that serotonin facilitates GABA release in cortex via 5-HT2A receptors and that the functional response of this system is resistant to serotonin depletion.

Animals↗

PubMed1983

Transport and metabolism of gamma-aminobutyric acid in neurons and glia: implications for epilepsy.

One of the defects in human epilepsy appears to be the suboptimal functioning of at least certain central gamma-aminobutyric acid (GABA)-mediated synapses. Of the several approaches for the manipulation of the functional state of such synapses that have been investigated, the possibility of interference with GABA metabolism and GABA transport processes is reviewed. It is concluded that the efficiency of inhibitors of the GABA-metabolizing enzyme, GABA transaminase, as antiepileptic drugs is related to the ability of the inhibitors to increase selectively the synaptic or transmitter-related GABA levels. Whether or not this reflects different modes of action of these inhibitors on neuronal and glial GABA transaminase remains to be established. Inhibition of the GABA transport mechanisms seems to represent an alternative approach to increase synaptic GABA levels. Evidence is presented that inhibitors of glial GABA uptake possess anticonvulsant activity. A comparison of drugs that inhibit both neuronal and glial GABA uptake with selective glial GABA uptake inhibitors indicates that the latter type of inhibitor most effectively blocks seizure activity. Such a drug is 4,5,6,7-tetrahydroisoxazolo[4,5c]pyridin-3-ol (THPO), which unfortunately lacks the important property of easy penetration of the blood-brain barrier. Prodrugs of this glial-selective GABA uptake inhibitor may have pharmacological and therapeutic interest.

Biological Transport↗

PubMed1987

Regional mirex distribution and its effects on gamma-aminobutyric acid and flunitrazepam binding in mouse brains.

Following ip injection of [14C]mirex, its regional distribution was studied parallel to its in vitro effects on [3H]-gamma-aminobutyric acid (GABA) and [3H]flunitrazepam (FNZ) binding to, and [3H]GABA release from, synaptosomes of various mouse brain regions, in order to determine the relationship between relative mirex distribution and its neurotoxic effects mediated through the GABA receptor-ionophore complex. The pattern of mirex uptake into cerebral cortex (CC), brainstem (BS), and cerebellum (CB) showed an initial linear dose-dependent uptake, followed by a decline at higher concentration. The Vmax and Km values determined for the linear mirex uptake phase indicated varied affinities by brain regions, CB and BS being more susceptible to mirex uptake than CC. Both synaptosomal GABA binding and FNZ binding were significantly reduced by mirex in the order of BS approximately equal to CB greater than CC for GABA, and BS approximately equal to CC greater than CB for FNZ. However, mirex lacked any significant effect on the Ca2+-dependent, K+-stimulated release of GABA from radio-prelabeled synaptosomes. While the data indicate no significant differences between brain regions in mirex uptake, they suggest that regional specificities do exist with respect to the inhibition caused by mirex on GABA and FNZ binding to synaptosomes. Unlike the major effects of chlordecone (an analog of mirex) on the dopaminergic system, mirex seems to be primarily neurotoxic through its more specific interaction with the GABA and FNZ binding sites.

Animals↗

PubMed1996

Allosteric uncoupling after chronic benzodiazepine exposure of recombinant gamma-aminobutyric acid(A) receptors expressed in Sf9 cells: ligand efficacy and subtype selectivity.

By using the baculovirus expression system, we report decreases in allosteric coupling at individual gamma-aminobutyric acid (GABA)(A) receptor subtypes (alpha-1, beta-2 and gamma-2, alpha-2, beta-3 and gamma-2 and alpha-5, beta-3 and gamma-2) after chronic benzodiazepine exposure that replicate coupling changes measured in rat cortical membranes after in vivo benzodiazepine exposure. The appearance of uncoupling was time-dependent and the magnitude of uncoupling at expressed GABA(A) receptor subtypes after chronic exposure was dependent upon the efficacy of the ligand in a subtype-specific manner. In addition, the expression of uncoupling was not accompanied by changes in benzodiazepine receptor number or affinity at any expressed GABA(A) subtype examined. The specificity of the coupling change was further shown by the ability of a brief exposure to the benzodiazepine receptor antagonist, Ro15-1788, to reverse the uncoupling induced by chronic benzodiazepine exposure. These findings suggest that alterations at the GABA(A) receptor complex after chronic benzodiazepine exposure are mediated directly by agonist effects at the GABA(A) receptor complex and are not the product of the changes in the surrounding neuronal environment. Furthermore, the present study shows that drug efficacy, and not simply affinity, plays a critical role in determining the degree of uncoupling, and perhaps, in the development of tolerance and dependence.

Allosteric Regulation↗

PubMed1986

Morphine and norepinephrine but not 5-hydroxytryptamine and gamma-aminobutyric acid inhibit the potassium-stimulated release of substance P from rat spinal cord slices.

We studied whether morphine, norepinephrine (NE), 5-hydroxytryptamine (5-HT) and gamma-aminobutyric acid (GABA) inhibit the potassium-stimulated release of substance P (SP) from rat spinal cord slices. Male Sprague-Dawley rats were decapitated and a 2-cm segment of lumbosacral spinal cord was removed, chopped into 0.5 X 0.5 mm pieces, weighed, placed in a perfusion chamber and perfused at 37 degrees C with a modified Krebs bicarbonate buffer. Perfusate was collected, lyophilized, then assayed for SP using radioimmunoassay. Exposure of spinal cord tissue to 50 mM KCl for 8 min produced a calcium-dependent increase in the release of SP from a basal level of approximately 0.1 pg/mg tissue/min to 0.3 pg/mg tissue/min. Morphine and NE at concentrations of 10(-4) and 10(-5) M did not alter basal release but caused a significant reduction in the potassium-stimulated release of SP. Naloxone (10(-5) M) and phentolamine (10(-5) M) did not affect SP release but attenuated the effects of morphine and NE, respectively. Naloxone did not antagonize the inhibition of release produced by NE nor did phentolamine block the effect of morphine, suggesting that the actions of the agonists are independent. In contrast, 5-HT and GABA at concentrations of 10(-4) M and 10(-5) M did not significantly alter the basal or potassium-stimulated release of SP. These results demonstrate a differential regulation of SP release in the spinal cord and support the hypothesis that morphine and NE may modify nociception, in part, by inhibiting the release of SP in the spinal cord.

Animals↗

PubMed2006

Thyroid hormone and gamma-aminobutyric acid (GABA) interactions in neuroendocrine systems.

Thyroid hormones (THs) have critical roles in brain development and normal brain function in vertebrates. Clinical evidence suggests that some human nervous disorders involving GABA(gamma-aminobutyric acid)-ergic systems are related to thyroid dysfunction (i.e. hyperthyroidism or hypothyroidism). There is experimental evidence from in vivo and in vitro studies on rats and mice indicating that THs have effects on multiple components of the GABA system. These include effects on enzyme activities responsible for synthesis and degradation of GABA, levels of glutamate and GABA, GABA release and reuptake, and GABA(A) receptor expression and function. In developing brain, hypothyroidism generally decreases enzyme activities and GABA levels whereas in adult brain, hypothyroidism generally increases enzyme activities and GABA levels. Hyperthyroidism does not always have the opposite effect. In vitro studies on adult brain have shown that THs enhance GABA release and inhibit GABA-reuptake by rapid, extranuclear actions, suggesting that presence of THs in the synapse could prolong the action of GABA after release. There are conflicting results on effects of long term changes in TH levels on GABA reuptake. Increasing and decreasing circulating TH levels experimentally in vivo alter density of GABA(A) receptor-binding sites for GABA and benzodiazepines in brain, but results vary from study to study, which may reflect important regional differences in the brain. There is substantial evidence that THs also have an extranuclear effect to inhibit GABA-stimulated Cl(-) currents by a non-competitive mechanism in vitro. The thyroid gland exhibits GABA transport mechanisms as well as enzyme activities for GABA synthesis and degradation, all of which are sensitive to thyroidal state. In rats and humans, GABA inhibits thyroid stimulating hormone (TSH) release from the pituitary, possibly by action directly on the pituitary or on hypothalamic thyrotropin-releasing hormone neurons. In mice, GABA inhibits TSH-stimulated TH release from the thyroid gland. Taken together, these studies provide strong support for the hypothesis that there is reciprocal regulation of the thyroid and GABA systems in vertebrates.

Animals↗

PubMed1999

Differential blockade of gamma-aminobutyric acid type A receptors by the neuroactive steroid dehydroepiandrosterone sulfate in posterior and intermediate pituitary.

Dehydroepiandrosterone sulfate (DHEAS) is a neuroactive steroid with antagonist action at gamma-aminobutyric acid type A (GABAA) receptors. Patch-clamp techniques were used to investigate DHEAS actions at GABAA receptors of the rat pituitary gland at two distinct loci: posterior pituitary nerve terminals and intermediate pituitary endocrine cells. The GABA responses in these two regions were quite different, with posterior pituitary responses having smaller amplitudes and desensitizing more rapidly and more completely. DHEAS blockade of GABAA receptors in the two regions also was different. In posterior pituitary, a site with an apparent dissociation constant of 15 microM accounted for most of the blockade, but a small fraction of blockade may be related to a site with a dissociation constant in the nanomolar range. In the intermediate lobe, DHEAS sensitivities in the nanomolar and micromolar ranges were clearly evident, in proportions that varied widely from cell to cell. Regardless of whether the GABA response of a cell was highly sensitive or weakly sensitive to DHEAS, GABA alone evoked currents that were indistinguishable in terms of amplitude, desensitization kinetics, and GABA sensitivity. Thus, the structural elements responsible for DHEAS blockade have a highly selective impact on receptor function. GABAA receptors with nanomolar sensitivity to DHEAS have not been described previously. This suggests that DHEAS may have an important role in the modulation of neuropeptide secretion, and the diverse properties of GABAA receptors in the rat pituitary provide mechanisms for selective regulation of the different peptidergic systems of this gland.

Animals↗

PubMed1998

A subclass of prefrontal gamma-aminobutyric acid axon terminals are selectively altered in schizophrenia.

In the primate cerebral cortex, morphologically and functionally diverse classes of local circuit neurons containing the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) differentially regulate the activity of pyramidal cells, the principal type of excitatory output neurons. In schizophrenia, GABA neurotransmission in the prefrontal cortex (PFC) appears to be disturbed but whether specific populations of GABA neurons are affected is not known. The chandelier class of GABA neurons are of particular interest because their axon terminals, which form distinctive arrays termed "cartridges," provide inhibitory input exclusively to the axon initial segment of pyramidal cells. Thus, chandelier cells are positioned to powerfully regulate the excitatory output of pyramidal neurons and, consequently, to substantially affect the patterns of neuronal activity within the PFC. In this study, an antibody directed against the GABA membrane transporter GAT-1 was used to label GABA axon terminals in postmortem human brains. The relative density of GAT-1-immunoreactive axon cartridges furnished by chandelier neurons was decreased by 40% in the PFC of schizophrenic subjects compared with matched groups of normal control and nonschizophrenic psychiatric subjects. In contrast, markers of the axon terminals of other populations of GABA neurons were not altered in the schizophrenic subjects. Furthermore, the density of GAT-1-immunoreactive axon cartridges was not altered in psychiatric subjects who had been treated with antipsychotic medications. The changes in GAT-1-immunoreactive axon cartridges of chandelier neurons in schizophrenia are likely to reflect altered information processing within the PFC and in its output connections to other brain regions and could contribute to the cognitive impairments seen in this disorder.

Autopsy↗

PubMed1986

Heterogeneity of [3H]ethyl beta-carboline-3-carboxylate binding sites and [3H]gamma-aminobutyric acid binding sites.

Binding properties of [3H]flunitrazepam ([3H]FNZ), [3H]ethyl beta-carboline-3-carboxylate ([3H]beta CCE), [3H]muscimol ([3H]MUSC) and [3H]gamma-aminobutyric acid ([3H]GABA) to bovine cortical membranes and to their Triton extracts were studied. GABA, 1 X 10(-5) M, stimulated [3H]FNZ binding of frozen, thawed and washed membranes by an increase in affinity without alteration of the maximal number of binding sites, and this GABA stimulated [3H]FNZ binding can be inhibited by bicuculline methobromide. Freeze, thaw and wash with Triton X-100 removed the low affinity [3H]MUSC binding sites. The ratios of [3H]FNZ binding sites to [3H]beta CCE binding sites and [3H]MUSC binding sites to [3H]GABA binding sites were always found to be about 1:2 in both membranes and soluble extracts. The fact that [3H]beta CCE, after displaced by clonazepam, can be further displaced by unlabelled beta CCE from its binding sites and that a portion of [3H]beta CCE binding sites can be survived from FNZ-photolysis implied that there are at least two subclasses of beta CCE binding sites, one is sensitive to beta CCE only and the other is sensitive to both beta CCE and benzodiazepines (BZs). [3H]GABA, after displaced by MUSC, can be further displaced by unlabelled GABA from its binding sites. The results also support that there are two subclasses of BZ-related GABA binding sites, one is sensitive to GABA only and the other is sensitive to both GABA and MUSC. Furthermore, the decay rates of [3H]beta CCE and [3H]GABA binding activities exposed to various degree of electron bombardment are identical, which is evident that these two binding sites are believed to be functional associated in a macromolecular complex with molecular mass about 220,000 Mr.

Animals↗

PubMed1989

Differences in the negative allosteric modulation of gamma-aminobutyric acid receptors elicited by 4'-chlorodiazepam and by a beta-carboline-3-carboxylate ester: a study with natural and reconstituted receptors.

Cl- currents elicited by gamma-aminobutyric acid (GABA) application were recorded with the whole-cell tight-seal technique from voltage-clamped cortical neurons of neonatal rats in primary culture. The peripheral benzodiazepine recognition site ligand 4'-chlorodiazepam [Ro 5-4864; 7-chloro-1,3-dihydro-1-methyl-5-(4-chlorophenyl)-2H-[1,4]-benzodiazep in-2- one] inhibited the GABA-generated currents in a dose-dependent manner. Also, a beta-carboline (DMCM; 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate methyl ester), acting as a negative allosteric modulator of GABAA receptors, reduced the intensity of GABA-generated currents with similar efficacy but greater potency. Flumazenil (Ro 15-1788; 8-fluro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo-[1,5-a] [1,4]-benzodiazepine-3-carboxylate ethyl ester) antagonized DMCM inhibition but not that elicited by 4'-chlorodiazepam. The isoquinoline carboxamide PK 11195, an antagonist of 4'-chlorodiazepam effects in other systems, failed to antagonize the action of 4'-chlorodiazepam. The transient expression of various molecular forms of GABAA receptors in the human embryonic kidney cell line 293 allowed a study of the minimal structural requirements for the inhibition of GABA-induced Cl- currents by bicuculline, picrotoxin, 4'-chlorodiazepam, and DMCM. GABA-elicited Cl- currents in cells coexpressing alpha 1 and beta 1 subunits of GABAA receptors were inhibited by bicuculline and picrotoxin, but not by DMCM or 4'-chlorodiazepam. Conversely, the GABA currents in cells coexpressing alpha 1 beta 1 and gamma 2 subunits were inhibited by bicuculline, picrotoxin, 4'-chlorodiazepam, and DMCM. Since the Cl- currents generated by GABA in some molecular forms of GABAA receptors are inhibited by bicuculline and picrotoxin only, 4'-chlorodiazepam cannot be acting isosterically with picrotoxin.

Animals↗

PubMed1998

The ontogenic appearance of tyrosine hydroxylase-, serotonin-, gamma-aminobutyric acid-, calcitonin gene-related peptide-, substance P-, and synaptophysin-immunoreactivity in rat pituitary gland.

The initial appearance of tyrosine hydroxylase (TH)-, serotonin (5-HT)-, gamma-aminobutyric acid (GABA)-, calcitonin gene-related peptide- (CGRP), substance P-, and synaptophysin-immunoreactivity in the rat pituitary gland, and in the related brain regions was investigated. Several groups of TH-immunoreactive neurons were first detected in the brain stem on day E17, and in the hypothalamus on day E18, followed by TH-immunoreactivity in the median eminence and infundibulum on E19-E20. TH-positive fibers appeared in the posterior lobe on day E20 and in the intermediate lobe on day P0. 5-HT-immunoreactivity was first detected on day E17 in neurons and nerve fibers in the brain stem and in the median eminence, respectively. On day E18, a few 5-HT-immunoreactive fibers were detected in the posterior lobe of the pituitary, although they were consistently seen in the infundibulum from day E19. In newborn rats, some 5-HT-immunoreactive fibers, but no neurons, were seen in the hypothalamus. GABA immunoreactivity appeared on day E17 in several nerve fibers of the infundibulum and the posterior lobe. Some neurons in the cortex and ventral hypothalamus transiently expressed GABA-immunoreactivity on day E17. In newborn rats, a plexus of GABA-immunoreactive fibers was detected for the first time in the intermediate lobe. No CGRP-immunoreactive fibers could be detected in the prenatal pituitary. On day P10, CGRP-immunoreactive fibers were first observed in the anterior lobe. Later their number considerably increased, while only sporadic fibers could be found in the intermediate or posterior lobes. No substance P-immunoreactivity could be detected in any of the lobes in the embryonic or developing postnatal rat pituitary, instead the adult anterior lobe occasionally showed some substance P-immunoreactive fibers. Synaptophysin-immunoreactivity was first detected in the posterior lobe on day E20, followed shortly by its expression in the intermediate lobe in newborn rats. The time course of GABA and 5-HT expression revealed in the present study suggests that these transmitters, which are initially expressed in the developing pituitary clearly before synaptic maturation, may act as trophic molecules during the prenatal period.

Animals↗

PubMed1990

[The effect of glycine and gamma-aminobutyric acid on the evoked activity of the spinal cord motor neurons in the lamprey].

The influence of bath application of glycine (10(-5)-10(-3) mol/l) and gamma-aminobutyric acid (10(-5)-10(-2) mol/l) on the monosynaptic EPSPs evoked in motoneurons by stimulation of a descending tract and individual Müller axons was studied in spinal cord-notochord preparation of lamprey (Lampetra fluviatilis). Both amino acids hyperpolarized the motoneuron membrane and depressed the evoked synaptic activity. But the inhibitory effect of glycine was stronger and it was revealed at lower concentrations as compared to that of GABA. It is concluded that glycine is more effective in blocking the postsynaptic motoneuron activity in comparison with GABA in the spinal cord of lamprey.

Animals↗

PubMed1977

gamma-Aminobutyric acid metabolism in subcellular particles of mouse brain and its relationship to convulsions.

The in vivo effects of convulsant drugs (hydrazine and penicillamine) on the metabolism of gamma-aminobutyric acid (GABA) in subcellular fractions of mouse brain were studied. Both substances inhibited the activity of glutamic acid decarboxylase [EC 4.1.1.15] (GAD) in the synaptosomal fraction (nerve ending particles) and reduced the concentration of GABA in the same fraction at the onset of convulsions, though changes in the total GABA concentration in the brain did not correlate with the onset of convulsions. Therefore, it is suggested that the concomitant decrease of GAD activity and GABA concentration in the nerve endings, independently of the total GABA concentration, is probably an important factor in the onset of some kinds of convulsions.

4-Aminobutyrate Transaminase↗

PubMed1980

Use of a synaptosomal model to monitor drug-induced in vivo changes in the gamma-aminobutyric acid content of nerve endings and its relevance to research on antipsychotic drugs.

The validity of a synaptosomal nuclei model to monitor drug-induced changes in the gamma-aminobutyric acid (GABA) content of nerve endings is reviewed. Examples of data obtained using the model are presented and the possibility of using the model for research on antipsychotic drugs is discussed.

Antipsychotic Agents↗