Mono N-Aryl ethylenediamine and piperazine derivatives are GABAA receptor blockers: Implications for psychiatry

@article{Squires2004MonoNE,
  title={Mono N-Aryl ethylenediamine and piperazine derivatives are GABAA receptor blockers: Implications for psychiatry},
  author={Richard Felt Squires and Else Saederup},
  journal={Neurochemical Research},
  year={2004},
  volume={18},
  pages={787-793}
}
Ethylenediamine (EDA) and piperazine are known GABA-A receptor agonists and this activity appears to reside in their carbamate adducts. In CO2-free incubation medium EDA and piperazine weakly reverse the inhibitory action of 1 μM GABA on specific, [35S]t-butylbicyclophosphorothionate (35S-TBPS) binding to rat brain membranes in vitro. In 25 mM sodium bicarbonate buffer, EDA and piperazine much more potently inhibit35S-TBPS binding in a way reversible by the GABA-A receptor blocker R5135. Thus… Expand
Subtype specificity of γ-aminobutyric acid type A receptor antagonism by clozapine
TLDR
The results indicate that clozapine antagonizes the function of most GABAA receptor subtypes, and that the interaction is determined by the interaction of the α and β subunit variants. Expand
Clozapine's Antipsychotic Effects do not Depend on Blockade of 5-HT3 Receptors
TLDR
It is speculated that the anxiolytic and sedative effects of clozapine and several other antipsychotic drugs may be due to selective blockade of α1β2γ2 GABAA receptors which are preferentially located on certain types of GABAergic interneurons (probably parvalbumin positive). Expand
Pitrazepin: Interactions with Transmitter Receptors of the Central and Peripheral Nervous Systems
Pitrazepin [3-(piperazinyl-1)-9H-dibenz(c.f)triazolo(4,5-a)azepin], is an N-aryl-piperazine derivative, whose heterocyclic structure is similar to that of atypical antipsychotics like clozapine. ThisExpand
Clozapine and Some Other Antipsychotic Drugs May Preferentially Block the Same Subset of GABAA Receptors
TLDR
The results with KW-1937 suggest that its 50% reversal largely corresponds to the reversal obtained with DMCM, but entirely nonadditive with Ro 5-4864, and that virtually all of the [35S]TBPS binding sites inhibited by 1 μM GABA are coupled to benzodiazepine binding sites. Expand
GABAA receptors as novel drug targets for treatment of mental disorders
A balance between excitatory and inhibitory neurotransmissions in brain is an essential factor for the proper function of the brain. The amino acid gamma-aminobutyric-acid (GABA) is considered as theExpand
GABA A receptors as novel drug targets for treatment of mental disorders
A balance between excitatory and inhibitory neurotransmissions in brain is an essential factor for the proper function of the brain. The amino acid gamma-aminobutyric-acid (GABA) is considered as theExpand
Piperazine Derivatives: A Review of Activity on Neurotransmitter Receptors
Piperazine is a vital organic scaffold that consists of a six-membered ring containing two nitrogen atoms at opposite positions in the ring and also posse’s four carbon atoms. This moiety can beExpand
Investigation on the inclusion interaction of 4-sulfonatocalix[n]arenes with 1-(4-nitrophenyl)piperazine.
TLDR
1H NMR and molecular modeling studies were carried out and experimental results showed that the part of benzene ring of NPP penetrated into the hydrophobic cavity of SCXn, indicating that NPP could form the inclusion complex withSCXn. Expand
Intentional Recreational Abuse of Quetiapine Compared to Other Second-generation Antipsychotics
TLDR
Quetiapine abuse is relatively common, and is abused far more often than any other second-generation antipsychotic, according to the National Poison Data System (NPDS). Expand
The limited utility of electrocardiography variables used to predict arrhythmia in psychotropic drug overdose
TLDR
ECG measurements were generally weakly related to the occurrence of arrhythmia and should not be used as the sole criteria for risk assessment in tricyclic antidepressant overdose. Expand
...
1
2
...

References

SHOWING 1-10 OF 36 REFERENCES
Antidepressants and metabolites that block GABAA receptors coupled to 35S-t-butylbicyclophosphorothionate binding sites in rat brain
TLDR
It is speculated that selective blockade of excessive GABAergic inhibition of reward systems may contribute to the clinical effects of many antidepressants, in some cases via active metabolites. Expand
GABAA receptor blockers reverse the inhibitory effect of GABA on brain-specific [35S]TBPS binding
TLDR
Reversal of GABA-induced suppression of [35S]TBPS binding provides a simple method for further characterizing GABAA receptors linked to TBPS binding sites, and facilitates identification of convulsants and novel, perhaps selective, GABA antagonists. Expand
Importance of a novel GABAA receptor subunit for benzodiazepine pharmacology
TLDR
The isolation of a cloned cDNA encoding a new GABAA receptor subunit, termed γ2, which shares approximately 40% sequence identity with α-and β-subunits and whose messenger RNA is prominently localized in neuronal subpopulations throughout the CNS. Expand
Cerebellar GABAA receptor selective for a behavioural alcohol antagonist
TLDR
It is concluded that this α-subunit is part of a cerebellar receptor subtype, selective for Rol5-4513 (refs 17, 18), an antagonist of alcohol-induced motor incoordination and ataxia, and photoaffinity-labelled with benzodiazepines. Expand
m-Chlorophenylpiperazine as a probe of serotonin function
TLDR
mCPP is a safe, reliable, direct 5-hydroxytryptamine (5HT) agonist, which may be used to evaluate 5HT receptor sensitivity, which causes a consistent, dose-dependent elevation of ACTH, cortisol, and prolactin levels in both animals and humans, as well as increased body temperature in man. Expand
Structural and functional basis for GABAA receptor heterogeneity
TLDR
Two additional cDNAs encoding two additional GABAA receptor α-subunits are isolated, confirming the heterogeneous nature of the receptor/chloride channel complex and demonstrating the molecular basis for it. Expand
A COMPARATIVE STUDY OF THE ACTION OF γ‐AMINOBUTYRIC ACID AND PIPERAZINE ON THE LOBSTER MUSCLE FIBRE AND THE FROG SPINAL CORD
1 The effects of γ‐aminobutyric acid (GABA) and piperazine were compared on two in vitro preparations, the lobster muscle fibre and the frog spinal cord. 2 Both GABA and piperazine increased theExpand
Type I and type II GABAA-benzodiazepine receptors produced in transfected cells.
TLDR
Diversity in benzodiazepine pharmacology is generated by heterogeneity of the alpha subunit of the GABAA receptor, indicating that there are subtypes within the type II class. Expand
Iontophoretic studies on rat hippocampus with some novel GABA antagonists.
TLDR
The results are consistent with the existence of several GABA-A receptor types in brain, only some of which are blocked by certain partial reversers. Expand
Effects of m-chlorophenylpiperazine in normal subjects: a dose-response study.
m-Chlorophenylpiperazine (MCPP), a direct 5HT receptor agonist, was administered orally to 20 normal subjects in two doses (0.25 and 0.5 mg/kg) in a placebo-controlled design. Behavioral responses;Expand
...
1
2
3
4
...