GABA agonists and antagonists

Kerr, Donald; Ong, Jennifer

doi:10.1002/med.2610120604

Cited by 86 publications

(31 citation statements)

References 234 publications

(39 reference statements)

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“…Therefore, we can hypothesize that GVG abolishes the action of nicotine via its increase in GABA levels, which subsequently stimulates GABA B receptors. This is consistent with data indicating that the administration of baclofen, a selective GABA B agonist (Bowery and Pratt, 1992;Kerr et al, 1990), into the VTA significantly attenuates the CPP response in animals produced by systemic morphine (Tsuji et al, 1995). Furthermore, systemic administration of baclofen attenuates cocaine self-administration in rats on either progressive ratio or discrete trials reinforcement schedules (Roberts et al, 1996;Roberts and Andrews, 1997).…”

Section: Treatment Pairingssupporting

confidence: 90%

A pharmacologic strategy for the treatment of nicotine addiction

Dewey

Brodie

Gerasimov

et al. 1999

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159

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Like many psychostimulant drugs, nicotine elevates extracellular and synaptic dopamine (DA) concentrations in the nucleus accumbens (NAc). This elevation has been linked to its reinforcing properties. Dopaminergic transmission within the NAc is modulated by gamma-aminobutyric acid (GABA). Therefore, we examined the utility of gamma vinyl-GABA (GVG, Vigabatrin) for inhibiting nicotine's biochemical effects on NAc DA as well as its effects on behaviors associated with these biochemical changes. Given 2.5 hours prior to nicotine, GVG (75 mg/kg) had no effect on nicotine-induced increases in extracellular NAc DA. However, at 90 mg/kg, GVG significantly inhibited nicotine-induced increases by approximately 50% while at 100 or 150 mg/kg, GVG completely abolished nicotine-induced increases in both naive and chronically nicotine-treated animals. When given 12 or 24 hours prior to nicotine administration at a dose of 100 mg/kg, GVG-induced inhibition was diminished or abolished, respectively. In addition, at a dose of 18.75 mg/kg GVG abolished the expression of nicotine-induced conditioned place preference (CPP) while a dose of 75 mg/kg abolished the acquisition phase of CPP. Finally, using positron emission tomography (PET) and 11C-raclopride in primates, GVG (100 mg/kg) abolished nicotine-induced increases in synaptic DA while having no effect on the rate of metabolism of the radiotracer or its regional distribution. Together, these data suggest that GVG may be useful for the treatment of nicotine addiction and further support the strategy of targeting the GABAergic system with a suicide inhibitor of GABA-transaminase for the treatment of drug addiction.

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Section: Treatment Pairingssupporting

confidence: 90%

A pharmacologic strategy for the treatment of nicotine addiction

Dewey

Brodie

Gerasimov

et al. 1999

Synapse

159

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“…All these drugs mediate their CNS effects through interaction with the GABA A receptor complex by potentiation of inhibitory activities of GABA [for reviews, see [12][13][14]. While most of the compounds are synthetic [13,15,16], a range of plant-derived compounds interacted with GABA A receptor complex with diverse properties [for reviews, see 3,17].…”

Section: Discussionmentioning

confidence: 99%

Honokiol and Magnolol Selectively Interact with GABA<sub>A</sub> Receptor Subtypes in vitro

Wang²,

Nielsen³

2001

Pharmacology

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Honokiol and magnolol have been identified as modulators of the GABA_A receptors in vitro. Our previous study suggested a possible selectivity of honokiol and magnolol on GABA_Areceptor subtypes. This possibility was examined in the current study by ³H-muscimol and ³H-flunitrazepam binding assays on various rat brain membrane preparations and human recombinant GABA_A receptor subunit combinations expressed by the Sf-9/baculovirus system. Generally, honokiol and magnolol have a similar enhancing effect on ³H-muscimol binding to various membrane preparations in nonsaturation binding assays. Honokiol and magnolol preferentially increased ³H-muscimol binding to hippocampus compared to cortex and cerebellum (with a maximum enhancement of 400% of control). As for subunit combinations, honokiol and magnolol have a more potent enhancing effect on α₂ subunit containing combinations (with a maximum enhancement of 400–450% of control). This action was independent of the γ subunit. In saturation binding assays, magnolol affected either the number of binding sites (ca. 4-fold on α₂ containing combinations) or the binding affinity (on α₁ containing combinations) of ³H-muscimol binding to various GABA_A receptor subunit combinations. In contrast, honokiol increased only binding sites on α₂β₃γ_2s and α₂β₃ combinations, but both the number of binding sites and the binding affinity on α₁β₂γ_2S and α₁β₂ combinations. These results indicate that honokiol and magnolol have some selectivity on different GABA_A receptor subtypes. The property of interacting with GABA_A receptors and their selectivity could be responsible for the reported in vivo effects of these two compounds.

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“…Many [ 3 H]GABA and GABA analogues such as muscimol act as agonists for this site, and bicuculline acts as an antagonist. 152,153 The PTZinduced seizure test, also known as the s.c.Met (subcutaneous metrazole) test, is the standard test for identification of anticonvulsant activity in compounds that enhance GABAergic neurotransmission. Since the clinical aspects of certain generalized seizures, especially absence seizures, are highly correlated with experimental seizures produced in the s.c.Met model, compounds that afford protection in this model may be particularly useful in the treatment of absence seizures.…”

Section: Gaba a Receptorsmentioning

confidence: 99%