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Pharmaceuticals

Pharmaceuticals -> Listed in ZINC15

Warning

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]

P264, P270, P273, P301+P317, P330, P391, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 41 reports by companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Danger

H361: Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]

Acute Tox. 4 (100%)

Reproductive toxicity - Category 2, Additional category: Effects on or via lactation

N - Nervous system

QN - Nervous system

In preclinical studies, zotepine is characterized by the presence of a strong antiserotonergic activity when compared with other neuroleptic drugs. It has also been reported to present elevations in the seizure threshold in the amygdaloid nucleus. When zotepine's effects were analyzed by electroencephalography, it was noted a typical response of a low-potency neuroleptics of the sedative type. Administration of zotepine has shown improvements in numerical movements and complex reaction. These effects tend to be accompanied by increases in pulse rate, increase in prolactin levels and some typical neuroleptic side effects.

Zotepine is a dopamine antagonist that has a high affinity for D1- and D2-like receptors. It presents a strong antagonism for several serotonin receptors, such as 5-HT2a, 5-HT2c, 5-HT6 and 5-HT7. Zotepine activities are also related to the inhibition of noradrenaline reuptake and serotonergic activity. All these effects allow zotepine to improve the negative and cognitive symptoms of schizophrenia.

Zotepine is well metabolized in the body, it actually undergoes extensive first-pass metabolism to the metabolite norzotepine and several inactive metabolites. The main enzymes involved in zotepine metabolism are CYP1A2 and CYP3A4. Some of the main metabolic pathways include N-demethylation and oxygenation of N or S atoms, hydroxylation of the aromatic ring and consecutive conjugation.

Zotepine has known human metabolites that include 2-hydroxy-zotepine, Norzotepine, Zotepine -oxide, 3-hydroxy-zotepine, and Zotepine N-oxide.

Agents that control agitated psychotic behavior, alleviate acute psychotic states, reduce psychotic symptoms, and exert a quieting effect. They are used in SCHIZOPHRENIA; senile dementia; transient psychosis following surgery; or MYOCARDIAL INFARCTION; etc. These drugs are often referred to as neuroleptics alluding to the tendency to produce neurological side effects, but not all antipsychotics are likely to produce such effects. Many of these drugs may also be effective against nausea, emesis, and pruritus.

Preclinical pharmacokinetic studies have shown a dose-dependent increase in plasma levels with a tmax between 2-4 hours and Cmax from 6.9-19.6 ng/ml when administered in a dose of 25-100 mg of zotepine. The maximum concentration peaks and slow declines thereafter. When administered orally in preclinical studies, zotepine was proven to be absorbed rapidly and almost completely from the gastrointestinal tract.The unchanged drug and metabolites are rapidly distributed to the tissues.

Only small amounts of the unchanged zotepine are excreted in the urine and fecal excretion through the bile is the main route of elimination of both the unchanged drug and its metabolites.

The apparent volume of distribution of zotepine is 109 L/kg.

The apparent oral clearance of zotepine is 4.6 mg/h.kg.