Pathways

Zolpidem is a sedative hypnotic used for the short-term treatment of insomnia to improve sleep latency. Zolpidem binds on the benzodiazepine receptors in the post-synaptic GABA-A ligand-gated chloride channel in different sites of the central nervous system (CNS). This binding will result in an increase on the GABA inhibitory effects which is translated as an increase in the flow of chloride ions into the cell causing hyperpolarization and stabilization of the cellular plasma membrane. Zolpidem binding to the GABAA receptor chloride channel macromolecular complex is thought to lead to the sedative, anticonvulsant, anxiolytic, and myorelaxant drug effects of the drug.

Metabolites of Zolpidem are predicted with biotransformer.

Zonisamide is a sulfonamide anticonvulsant used to treat partial seizures. It can be found under the brand names Zonegran and Zonisade and is administered as an oral capsule. Zonisamide is a sulfonamide anticonvulsant used as an adjunctive therapy in adults with partial-onset seizures. Zonisamide may act by blocking repetitive firing of voltage-gated sodium channels, leading to a reduction of T-type calcium channel currents. By stopping the spread of seizure discharges, zonisamide prevents the extensor component of tonic convulsion, restricts the spread of focal seizures and prevents the propagation of seizures from the cortex to subcortical structures. The mechanism of action by which zonisamide controls seizures has not been fully established. However, its antiepileptic properties may be due to its effects on sodium and calcium channels. Zonisamide blocks sodium channels and reduces voltage-dependent, transient inward currents, stabilizing neuronal membranes and suppressing neuronal hypersynchronization. It affects T-type calcium currents, but has no effect on L-type calcium currents. Zonisamide suppresses synaptically-driven electrical activity by altering the synthesis, release, and degradation of neurotransmitters, such as glutamate. The use of zonisamide may lead to potentially fatal reactions. Severe reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, and aplastic anemia have been reported in patients treated with sulfonamides such as zonisamide. Zonisamide may also lead to the development of serious hematological events, drug reaction with eosinophilia and systemic symptoms (DRESS) and multi-organ hypersensitivity, acute myopia and secondary angle closure glaucoma, as well as suicidal behaviour and ideation.

Metabolites of Zonisamide are predicted with biotransformer.

Zopiclone, a nonbenzodiazepine hypnotic belonging to the pyrazolopyrimidine class, is employed for the short-term management of insomnia. Operating outside the benzodiazepine and barbiturate realms, it interacts with the gamma-aminobutyric acid-benzodiazepine (GABABZ) receptor complex, demonstrating both benzodiazepine-like and some barbiturate-like properties. By selectively binding to the brain alpha subunit of the GABA A omega-1 receptor, zopiclone's action unfolds through engagement with the benzodiazepine receptor complex and modulation of the GABABZ receptor chloride channel macromolecular complex. Its effects align with those of benzodiazepines, acting as full agonists on various GABAA receptor subunits (α1, α2, α3, α5), amplifying GABA's inhibitory actions to produce therapeutic (hypnotic and anxiolytic) and adverse outcomes. Primarily metabolized through processes like decarboxylation, demethylation, and side chain oxidation in the liver, zopiclone undergoes substantial metabolic transformation. This results in the formation of metabolites such as a weakly active N-oxide derivative (constituting around 12% of the dose) and an inactive N-desmethyl metabolite (approximately 16% of the dose). Moreover, nearly 50% of the dose is converted to additional inactive metabolites via decarboxylation, with hepatic microsomal enzymes seemingly playing no significant role in zopiclone clearance. Renowned for its distinct mechanism within the realm of nonbenzodiazepine hypnotics, zopiclone effectively addresses short-term insomnia management.

Metabolites of Zopiclone are predicted with biotransformer.