Etoperidone, trazodone and MCPP: in vitro and in vivo identification of serotonin 5-HT1A (antagonistic) activity

  title={Etoperidone, trazodone and MCPP: in vitro and in vivo identification of serotonin 5-HT1A (antagonistic) activity},
  author={Robert B Raffa and Richard P. Shank and Jeffry L. Vaught},
The Ki values for etoperidone, trazodone and MCPP (m-chlorophenylpiperazine dihydrochloride) at 5-HT1A sites (using rat cerebral cortical synaptosomes and [3H]8-OH-DPAT) were determined to be 20.2, 23.6 and 18.9 nM, respectively. In an effort to elucidate the functional nature of the interaction at 5-HT1A sites in vivo, the ability of each compound to elicit reciprocal forepaw treading (RFT) or to block the RFT induced by 8-OH-DPAT in reserpinized rats was tested. Specifically, 8-OH-DPAT (1.0… 

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

The agonist properties of trazodone and its active metabolite, m-chlorophenylpiperazine (m-CPP), at 5-HT1A receptors are elucidated by means of the guanosine-5′-O-(3-[ 35S]thio)-triphosphate ([35S]GTPγS) binding assay.

Daily administration ofm-chlorophenylpiperazine to healthy human volunteers rapidly attenuates many of its behavioral, hormonal, cardiovascular and temperature effects

Psychological and physical symptoms of anxiety, temperature, pupil size, diastolic blood pressure, and plasma ACTH, cortisol, and prolactin concentrations were increased by the first administration ofm-CPP compared to placebo, and all of these responses were attenuated onm- CPP days 2 and 3.

Behavioural and Neurochemical Consequences of MDMA Self-Administration in Rats

The findings are not consistent with the idea that the 5HT₁ₐ autoreceptor became supersensitive as a result of MDMA exposure, and it is therefore not a viable pharmacological target for restoring tissue levels of 5HT.

Effects of ipsapirone in healthy subjects: a dose-response study

IPS at 20 mg PO appears a useful probe to test 5HT1a function when temperature and cortisol are used as response variables and overall it had no significant effect on these parameters.

Mechanism of Action of Trazodone: a Multifunctional Drug

  • S. Stahl
  • Psychology, Biology
    CNS Spectrums
  • 2009
Although trazodone has traditionally been used as a low dose hypnotic, a new controlled release formulation that has the potential to improve the tolerability of high doses may provide an opportunity to revisit this multifunctional drug as an antidepressant as well.

[Personalized medicine with extended-release trazodone and/or once-a-day trazodone: from research trials to clinical practice].

The different formulations of trazodone allow a personalization of the treatment, which may be targeted to the specific needs of each patient, as well as identifying the characteristics of patients that may benefit from the use of one of the formulations.

[Multimodal serotonergic antidepressants].

  • D. S. Danilov
  • Psychology
    Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova
  • 2017
The data presented suggest the rationale for unifying all selective serotonergic antidepressants, simultaneously inhibiting the serotonin reuptake and directly interacting with serotonin receptors, in one group of 'multimodal serotonergy antidepressants'.

[Personalized treatment of depression phenotypes: role of trazodone in depression with insomnia].

Trazodone is efficacious for the treatment of a broad array of depressive symptoms and is particularly useful for patients presenting with insomnia as one of the symptoms of depression.

Pharmacological Study on Some New 3-[(1-Methylpyrrol-2-yl)- methyl]-4-Substituted 4,5-Dihydro-1H-1,2,4-triazol-5-ones

3-[(1-Methylpyrrol-2-yl)methyl]-4-substituted 4,5-dihydro-1H-1,2,4-triazol-5-ones and the effects of the synthesized compounds of the central nervous system of mice were studied.



A comparative pharmacological study of trazodone, etoperidone and 1-(m-chlorophenyl)piperazine.

Since 1-(m-chlorophenyl)piperazine (mCPP) is a metabolite of trazodone (TRZ) and etoperidone (ETO), two atypical antidepressants, a pharmacological study was undertaken to establish the possible

Trazodone, a central serotonin antagonist and agonist

It is indicated that TR has a double effect on the central 5-HT system: at low doses it acts as a5-HT antagonist, whereas at higher ones-as a 5- HT agonist, and the latter effect may be connected with formation of a metabolite, CPP, or a compound chemically related to CPP.

1‐m‐Chlorophenylpiperazine is an active metabolite common to the psychotropic drugs trazodone, etoperidone and mepiprazole

Data suggest that mCPP contributes to, or even accounts for, the antidepressant action of the parent drug trazodone.

The effect of etoperidone, a new potential antidepressant drug, on the central serotonin system

The above findings indicate that etoperidone has a biphasic action on the serotonergic transmission, revealing characteristics of the 5-HT antagonist and agonist.

Inhibitory effects of etoperidone on the spontaneous activity of brainstem neurones and their excitatory responses to some putative transmitters.

All the excitatory neuronal responses to ACh, 5 HT and NA (interpreted respectively as nicotinic cholinergic, alpha-noradrenergic, 5HT3-serotonergic) were blocked by ET, while the inhibitory responses to 5HT, NA and GABA were not affected.

(—)‐m‐Chlorophenyl‐piperazine, a central 5‐hydroxytryptamine agonist, is a metabolite of trazodone

binding sites, particularly on a brain regional basis, and Fillion, G., Rousselle, J.-C., Fillion, M.-P., Beaudoin, may confirm the existence of separate S-HT receptors. D. M., Goiny, M. R., Deniau.

Pharmacological properties of AF 1161, a new psychotropic drug.