Serotonin releasing agents Neurochemical, therapeutic and adverse effects

@article{Rothman2002SerotoninRA,
  title={Serotonin releasing agents Neurochemical, therapeutic and adverse effects},
  author={Richard B. Rothman and Michael H Baumann},
  journal={Pharmacology Biochemistry and Behavior},
  year={2002},
  volume={71},
  pages={825-836}
}
This review summarizes the neurochemical, therapeutic and adverse effects of serotonin (5-HT) releasing agents. The 5-HT releaser (plus minus)-fenfluramine is composed of two stereoisomers, (+)-fenfluramine and (minus sign)-fenfluramine, which are N-de-ethylated to yield the metabolites, (+)-norfenfluramine and (minus sign)-norfenfluramine. Fenfluramines and norfenfluramines are 5-HT transporter substrates and potent 5-HT releasers. Other 5-HT releasing agents include m-chlorophenylpiperazine… Expand
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References

SHOWING 1-10 OF 118 REFERENCES
Serotonin-releasing effects of substituted piperazines in vitro.
TLDR
These studies show that several piperazine-containing compounds can evoke a potent release of endogenous stores of hypothalamic 5-HT in vitro, actions which should be considered together with their direct agonist activity when interpreting the CNS effects in vivo. Expand
In vivo criteria to differentiate monoamine reuptake inhibitors from releasing agents: sibutramine is a reuptake inhibitor.
TLDR
Using microdialysis in the hypothalamus of unanesthetized rats, evidence is provided that serotonin- (5-HT) selective and nonselective reuptake inhibitors can be distinguished from the 5-HT-releasing agent fenfluramine by four criteria. Expand
1-(m-Chlorophenyl)piperazine (mCPP) Dissociates In Vivo Serotonin Release from Long-Term Serotonin Depletion in Rat Brain
TLDR
The notion that 5- HT release per se may not be sufficient to produce the long-term 5-HT deficits associated with d-fenfluramine and other amphetamines is supported. Expand
Neurochemical mechanism of action of drugs which modify feeding via the serotoninergic system
TLDR
Several studies with drugs affecting different serotonin mechanisms suggest that increase serotonin release and direct stimulation of postsynaptic receptors are the most effective mechanisms for causing depression of food intake, although inhibition of serotonin uptake may also contribute in appropriate conditions. Expand
The serotonin agonist m-chlorophenylpiperazine (mCPP) binds to serotonin transporter sites in human brain.
TLDR
It is demonstrated that mCPP also displays appreciable affinity for 5-HT transporters labeled by [125I]3 beta-(4-iodophenyl)tropan-2 beta-carboxylic acid methyl ester in human occipital cortex. Expand
Neurochemical mechanisms of phentermine and fenfluramine: Therapeutic and adverse effects
TLDR
The feasibility of developing novel drugs that produce the same neurochemical effects as phentermine plus fenfluramine, without the associated adverse effects of primary pulmonary hypertension, neurotoxicity, and abuse liability is discussed. Expand
Possible role of valvular serotonin 5-HT(2B) receptors in the cardiopathy associated with fenfluramine.
TLDR
It is proposed that preferential stimulation of valvular 5-HT(2B) receptors by norfenfluramine, ergot drugs, or5-HT released from carcinoid tumors (with or without accompanying 5- HT(2A) receptor activation) may contribute to valvial fibroplasia in humans. Expand
Intravenous administration of the serotonin agonist m-chlorophenylpiperazine (mCPP) increases extracellular serotonin in the diencephalon of awake rats
TLDR
Results indicate that mCPP increases extracellular 5-HT in rat brain by a presynaptic mechanism involving5-HT transporters, and suggest the possibility that m CPP exhibits indirect agonist properties in human brain. Expand
Aminorex, fenfluramine, and chlorphentermine are serotonin transporter substrates. Implications for primary pulmonary hypertension.
TLDR
It is speculated that medications that are 5-HT transporter substrates get translocated into pulmonary cells where, depending on the degree of drug retention, their intrinsic drug toxicity, and individual susceptibility, PPH could develop as a response to high levels of these drugs or metabolites. Expand
Evidence for Possible Involvement of 5-HT2B Receptors in the Cardiac Valvulopathy Associated With Fenfluramine and Other Serotonergic Medications
TLDR
It is suggested that all clinically available medications with serotonergic activity and their active metabolites be screened for agonist activity at 5-HT2B receptors and that clinicians should consider suspending their use of medications with significant activity at5-HT1B receptors. Expand
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