Nefazodone is a pharmacological agent that is used in the treatment of depression. The substance belongs to the group of so-called dual-serotonergic antidepressants. Nefazodone is a phenylpiperazine derivative and, in terms of its structure and, to some extent, its action, it shows similarities to the antidepressant trazodone, which was discovered earlier.
What is nefazodone?
Nefazodone is a pharmacological agent used in the treatment of depression. Nefazodone is an active ingredient that belongs to the group of serotonin–norepinephrine reuptake inhibitors. This makes it one of the antidepressants. Due to serious liver-toxic side effects, nefazodone is no longer marketed today. Previously, the drug was available in Germany from 1997 under the trade name Nefadar. Several cases of severe liver failure resulted in the withdrawal of the drug nefazodone from the market in Germany in 2003. In principle, the pharmacological use of the substance nefazodone is as nefazodone hydrochloride. This is a crystalline powder of white color, which has a low solubility in water. Nefazodone is a derivative of triazole and phenylpiperazine. It also has structural similarities to the substance trazodone.
Pharmacologic Action
Nefazodone is an antidepressant whose exact mechanism of action has not been fully elucidated. In any case, the interaction with so-called serotoninergic mechanisms is relevant. This is because nefazodone has a twofold effect on serotoninergic neurotransmissions. On the one hand, the substance reduces specific postsynaptic receptors that are designed for serotonin. On the other hand, nefazodone partially stops presynaptic uptake of the substance. Certain active metabolites also interfere with serotonin receptors. Also relevant to the effect is that nefazodone has no appreciable affinity for dopaminergic, histaminergic, and cholinergic receptors. In addition to serotonin, nefazodone also inhibits neuronal reuptake of the neurotransmitter norepinephrine. In addition, the drug nefazodone has hepatotoxic characteristics, which is why it has led to serious liver disease in some cases. The action at the serotonin receptor is primarily antagonistic. Thus, the concentration of monoamine increases. The concentration of serotonin only increases again when the responsible serotonin transporter is restricted. This is responsible for getting the monoamine out of the synaptic cleft again. Nefazodone thereby exerts its effect as an inhibitor of serotonin and its reuptake. In addition, nefazodone weakly inhibits certain enzymes, which is why it has fewer undesirable side effects than similar drugs in the same category, such as paroxetine and fluoxetine. The drug nefazodone is completely absorbed by gastrointestinal route and in a relatively short time. Maximum concentrations in blood plasma occur approximately two hours after ingestion. Since the presystemic metabolimus is very strong, the bioavailability of the pharmaceutical substance is only about 20 percent. It is therefore advisable to take the drug together with a meal, as under these circumstances the so-called systemic availability can increase by up to 18 percent. The drug nefazodone is metabolized in the liver with the help of the cytochrome CYP3A4. At the same time, this is a substance that strongly affects the cytochrome. The three active metabolites are the substances meta-chlorophenylpiperazine, hydroxynefazodone and triazoldione. However, hydroxynefazodone is of particular clinical importance. This substance is capable of reaching high concentrations and has similarities to nefazodone.
Medical application and use
The drug nefazodone is used for a number of mental illnesses. Primarily, it is a drug that is used in the treatment of depression. In addition, nefazodone is also prescribed, for example, for obsessive-compulsive disorder, borderline syndrome or panic attacks. The drug is usually taken orally. The bioavailability of the substance is around 20 percent. The active ingredient binds completely to plasma proteins in the blood.Nefazodone is excreted predominantly in the urine and minimally in the stool. If the dose of hydroxynefazodone is increased only slightly, disproportionately increased concentrations in plasma are the result. Basically, the plasma half-life of the two substances is about two hours and, after reintroduction, three and a half hours. In people who are over 65 years of age and those who suffer from impaired liver function, plasma levels are significantly higher than in patients who are young and without health impairments.
Risks and side effects
A number of diverse adverse side effects are possible in the course of taking nefazodone. These are partly dependent on the dose. For example, drowsiness, dizziness, nausea, and dry mouth sometimes occur. In addition, visual disturbances such as blurred vision are possible. In some cases, the symptoms gradually subside slightly with increasing duration of treatment. Less common side effects include withdrawal symptoms, hair loss, and hypoglycemia. In addition, sexual dysfunction is possible. In isolated cases, severe liver dysfunction has been observed and may continue for weeks or months after therapy. If nefazodone is taken together with MAO inhibitors, affected patients sometimes suffer from suicidal ideation.
