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PW176655

Pw176655 View Pathway
drug action

Zuclopenthixol H1 Antihistamine Smooth Muscle Relaxation Action Pathway

Homo sapiens
Zuclopenthixol is a weak H1-antihistamine. H1-antihistamines interfere with the agonist action of histamine at the H1 receptor and are administered to attenuate inflammatory process in order to treat conditions such as allergic rhinitis, allergic conjunctivitis, and urticaria. H1-antihistamines act on H1 receptors in T-cells to inhibit the immune response, in blood vessels to constrict dilated blood vessels, and in smooth muscles of lungs and intestines to relax those muscles. H1-antihistamines interfere with the agonist action of histamine at the H1 receptor and are administered to attenuate inflammatory process in order to treat conditions such as allergic rhinitis, allergic conjunctivitis, and urticaria. H1-antihistamines act on H1 receptors in T-cells to inhibit the immune response, in blood vessels to constrict dilated blood vessels, and in smooth muscles of lungs and intestines to relax those muscles. Allergies causes blood vessel dilation which causes swelling (edema) and fluid leakage. Zuclopenthixol also inhibits the H1 histamine receptor on bronchiole smooth muscle myocytes. This normally activates the Gq signalling cascade which activates phospholipase C which catalyzes the production of Inositol 1,4,5-trisphosphate (IP3) and Diacylglycerol (DAG). Because of the inhibition, IP3 doesn't activate the release of calcium from the sarcoplasmic reticulum, and DAG doesn't activate the release of calcium into the cytosol of the endothelial cell. This causes a low concentration of calcium in the cytosol, and it, therefore, cannot bind to calmodulin.Calcium bound calmodulin is required for the activation of myosin light chain kinase. This prevents the phosphorylation of myosin light chain 3, causing an accumulation of myosin light chain 3. This causes muscle relaxation, opening up the bronchioles in the lungs, making breathing easier.

PW147102

Pw147102 View Pathway
drug action

Zuclopenthixol H1 Antihistamine Neurological Sleep Action Pathway

Homo sapiens
Zuclopenthixol is an ethanolamine class H1 antihistamine used to treat insomnia and allergy symptoms such as hay fever and hives. It is also used with pyridoxine in the treatment of nausea and vomiting in pregnancy. H1-antihistamines interfere with the agonist action of histamine at the H1 receptor and are administered to attenuate inflammatory process in order to treat conditions such as allergic rhinitis, allergic conjunctivitis, and urticaria. Wakefulness is regulated by histamine in the tuberomammillary nucleus, a part of the hypothalamus. Histidine is decarboxylated into histamine in the neuron. Histamine is transported into synaptic vesicles by a monoamine transporter then released into the synapse. Normally histamine would activate the H1 histamine receptor on the post-synaptic neuron in the tuberomammillary nucleus. Zuclopenthixol inhibits the H1 histamine receptor, preventing the depolarization of the post-synaptic neuron. This prevents the wakefulness signal from being sent to the major areas of the brain, causing sleepiness.

PW145487

Pw145487 View Pathway
drug action

Zuclopenthixol Drug Metabolism Action Pathway

Homo sapiens

PW128180

Pw128180 View Pathway
drug action

Zuclopenthixol Dopamine Antagonist Action Pathway

Homo sapiens
Zuclopenthixol, also known as Zuclopentixol or Zuclopenthixolum, is an antipsychotic agent. Zuclopenthixol is a thioxanthene-based neuroleptic with therapeutic actions similar to the phenothiazine antipsychotics. Zuclopenthixol is a typical antipsychotic neuroleptic drug of the thioxanthene class. It mainly acts by antagonism of D1 and D2 dopamine receptors. Zuclopenthixol also has high affinity for alpha1-adrenergic and 5-HT2 receptors. It has weaker histamine H1 receptor blocking activity, and even lower affinity for muscarinic cholinergic and alpha2-adrenergic receptors.

PW145992

Pw145992 View Pathway
drug action

Zucapsaicin Drug Metabolism Action Pathway

Homo sapiens

PW146043

Pw146043 View Pathway
drug action

Zotepine Drug Metabolism Action Pathway

Homo sapiens

PW145285

Pw145285 View Pathway
drug action

Zopiclone Drug Metabolism Action Pathway

Homo sapiens

PW128437

Pw128437 View Pathway
drug action

Zopiclone Action Pathway

Homo sapiens
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.

PW145010

Pw145010 View Pathway
drug action

Zonisamide Drug Metabolism Action Pathway

Homo sapiens

PW128267

Pw128267 View Pathway
drug action

Zonisamide Action Pathway

Homo sapiens
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.