Trazodone and its active metabolite m-chlorophenylpiperazine as partial agonists at 5-HT1A receptors assessed by [35S]GTPγS binding

@article{Odagaki2005TrazodoneAI,
  title={Trazodone and its active metabolite m-chlorophenylpiperazine as partial agonists at 5-HT1A receptors assessed by [35S]GTP$\gamma$S binding},
  author={Yuji Odagaki and Ryoichi Toyoshima and Toshio Yamauchi},
  journal={Journal of Psychopharmacology},
  year={2005},
  volume={19},
  pages={235 - 241}
}
Trazodone is an effective antidepressant drug with a broad therapeutic spectrum, including anxiolytic efficacy. Although trazodone is usually referred to as a serotonin (5-HT) reuptake inhibitor, this pharmacological effect appears to be too weak to fully account for its clinical effectiveness. The present study aimed to elucidate the agonist properties of trazodone and its active metabolite, m-chlorophenylpiperazine (m-CPP), at 5-HT1A receptors by means of the guanosine-5′-O-(3-[35S]thio… 

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References

SHOWING 1-10 OF 49 REFERENCES
Biochemical investigations into the mode of action of trazodone
The antipsychotic aripiprazole is a potent, partial agonist at the human 5-HT1A receptor.
Piperazine derivatives including the putative anxiolytic drugs, buspirone and ipsapirone, are agonists at 5-HT1A receptors negatively coupled with adenylate cyclase in hippocampal neurons
TLDR
It is demonstrated that these piperazine based drugs act in both brain homogenate preparations and in intact neurons in a similar manner, and the biochemical models described here may aid in the development of even more active drugs in this class.
Trazodone is a potent agonist at 5-HT2C receptors mediating inhibition of the N-methyl-D-aspartate/nitric oxide/cyclic GMP pathway in rat cerebellum.
TLDR
It is concluded that trazodone behaves as a potent full agonist at the 5-HT2C receptor mediating inhibition of the cerebellar N-methyl-D-aspartate/nitric oxide/cyclic GMP system.
A comparison of trazodone and fluoxetine: implications for a serotonergic mechanis of antidepressant action
TLDR
The preclinical and clinical data suggest that trazodone acts as an antidepressant via antagonist action at 5-HT2/1C receptors, while fluoxetine likely acts as a antidepressant via inhibition of 5- HT uptake.
5-HT1A receptor activation and antidepressant-like effects: F 13714 has high efficacy and marked antidepressant potential.
Comparative effects of trazodone and tricyclic antidepressants on uptake of selected neurotransmitters by isolated rat brain synaptosomes
TLDR
Although less potent, trazodone was 4±0.6 times more selective than clomipramine in its ability to inhibit synaptosomal uptake of 5-HT with respect to NE, consistent with the clinical antidepressant efficacy of traZodone.
BIMT 17, a 5-HT2A receptor antagonist and 5-HT1A receptor full agonist in rat cerebral cortex
TLDR
It was concluded that BIMT 17 was the only compound that behaved as a full agonist with respect to the CAMP response in the cortex, while exerting concurrent agonism at 5-HT1A receptors and antagonism at5-HT2A receptors.
...
1
2
3
4
5
...