Browsing Pathways

Thioridazine is a trifluoro-methyl phenothiazine derivative. Thioridazine blocks postsynaptic mesolimbic dopaminergic D1 and D2 receptors in the brain; blocks alpha-adrenergic effect, depresses the release of hypothalamic and hypophyseal hormones and is believed to depress the reticular activating system thus affecting basal metabolism, body temperature, wakefulness, vasomotor tone, and emesis. Similar to other first-generation or typical antipsychotics, thioridazine is a medication used to treat schizophrenia. Other indications for use include other psychotic disorders, depressive disorders, pediatric behavioral disorders, and geriatric psychoneurotic manifestations. Positive symptoms are believed to manifest as a result of increased levels of dopamine in the mesolimbic pathway. More specifically, thioridazine blocks DA-2 receptors in the mesolimbic pathway, diminishing positive symptoms. Thioridazine is classified as a low potency first-generation antipsychotic, and as such, is relatively sedating. Thioridazine is a substrate of the hepatic enzyme CYP450 2D6 and is also an inhibitor of the same enzyme. The drug also exhibits activity at muscarinic receptors (most notably the M1 receptor), which is most likely the source of its anticholinergic effects (e.g., dry mouth, constipation, etc.), the alpha 1A adrenergic receptor (which may explain its association with orthostatic hypotension), the H1 histamine receptor (probably accounting for much of its sedating effect), and the hERG gene, which is likely responsible for its cardiotoxicity

Thiopental is a barbiturate utilized for inducing general anesthesia, managing convulsions, and reducing intracranial pressure. Administered intravenously, this barbiturate is employed to induce general anesthesia promptly, achieve temporary complete anesthesia, induce hypnosis, and control convulsive conditions. Notably, it has been employed in neurosurgical contexts to alleviate elevated intracranial pressure. Although it lacks excitatory effects, its analgesic and muscle relaxant properties are limited. It has been shown that low doses can counteract analgesia and lower the pain threshold. Thiopental finds application as the sole anesthetic for brief procedures, as an induction agent preceding other anesthetics, to supplement regional anesthesia, to provide hypnosis alongside other agents for analgesia or muscle relaxation, for managing convulsions during inhalation or local anesthesia, in neurosurgical cases with heightened intracranial pressure, and for narcoanalysis and narcosynthesis in psychiatric disorders. Functioning as an ultrashort-acting central nervous system depressant, thiopental induces rapid hypnosis and anesthesia, yet it lacks analgesic properties. Its binding to a specific site linked to a Cl- ionopore at the GABAA receptor extends the opening duration of the ionopore, thereby prolonging GABA's inhibitory effect in the thalamus. This results in prolonged post-synaptic inhibition. The drug's rapid binding to fatty tissues leads to anesthetic accumulation, producing prolonged effects due to gradual drug release.

Thioguanine is a purine antimetabolite prodrug closely related to mercaptopurine and similarly inhibits purine metabolism. The thioguanine pathway is shown as a part of the mercaptopurine pathway. Thioguanine exerts cytotoxic effects via incorporation of thiodeoxyguanosine triphosphate into DNA and thioguanosine triphosphate into RNA and inhibition of Ras-related C3 botulinum toxin substrate 1, which induces apoptosis of activated T cells. Once in a cell, thioguanine is converted to thioguanosine monophosphate by hypoxanthine-guanine phosphoribosyltransferase. Thioguanosine monophosphate is then phosphorylated to thioguanosine diphosphate, which is converted via a thiodeoxyguanosine diphosphate intermediate to thiodeoxyguanosine triphosphate. Thiodeoxyguanosine triphosphate is incorporated into DNA causing cytotoxicity. Thioguanosine diphosphate is also converted to thioguanosine triphosphate which is incorporated into RNA. The thioguanosine triphosphate metabolite also inhibits Ras-related C3 botulinum toxin substrate 1, a plasma membrane-associated small GTPase that regulates cellular processes, inducing apoptosis in activated T cells.

Thioguanine is an antineoplastic compound used to treat acute leukemia. It is usually administered orally and delivered to the site of action through the blood. Thioguanine has similar properties to 6-mercaptopurine as they share similar metabolites with the exception of 6-meraptopurine inhibiting the purine de novo synthesis pathway. Thioguanine's metabolites thiodeoxyguanosine-5'-triphosphate and thioguanosine 5'-triphosphate can be incorporated into DNA and RNA respectively which causes proliferation and protein synthesis to be inhibited. Thioguanosine 5'-triphosphate also inhibits ras-related C3 botulinum toxin substrate 1 a small GTPase membrane protein responsible for regulating cellular functions like cell growth, antimicrobial cytotoxicity, apoptosis regulation of lymphocytes. With ras-related C3 botulinum toxin substrate 1 being inhibited, apoptosis of T and B lymphocytes is no longer regulated and they are killed off. This leads to immunosuppression.

Thiocolchicoside is a semi-synthetic colchicine derivative used as skeletal muscle-relaxant drug used in the treatment of orthopedic, traumatic and rheumatologic disorders. It is indicated as an adjuvant drug in the treatment of painful muscle contractures and is indicated in acute spinal pathology, for adults and adolescents 16 years of age and older.thiocolchicoside 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. Thiocolchicoside has a selective and potent affinity for g-aminobutyric acid A (GABA-A) receptors and acts on muscular contractures by activating the GABA inhibitory pathways thereby behaving as a potent muscle relaxant. Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the human cortex. GABAergic neurons are involved in myorelaxation, anxiolytic treatment, sedation, and anesthetics.

Thiethylperazine is in the class of the piperazine - phenothiazines which are a class of first generation antipsychotic medications. Phenothiazines are generally dopamine receptor antagonists. Thiethylperazine' s antipsychotic effect is due to antagonism at dopamine and serotonin type 2 receptors, with greater activity at serotonin 5-HT2 receptors than at dopamine type-2 receptors. This may explain the lack of extrapyramidal effects. Thiethylperazine does not appear to block dopamine within the tubero-infundibular tract, explaining the lower incidence of hyperprolactinemia than with typical antipsychotic agents or risperidone. It is a sedating antihistamine used as an antiemetic agent for the control of nausea and vomiting associated with surgical procedures.