DDInter1042 DDInter853
Leuprolide is a synthetic 9-residue peptide analogue of gonadotropin-releasing hormone (GnRH). Unlike the endogenous decapeptide GnRH, leuprolide contains a single D-amino acid (D-leucyl) residue, which helps to increase its circulating half-life from three to four minutes to approximately three hours. As a GnRH mimic, leuprolide is capable of binding to the GnRH receptor (GnRHR) and inducing downstream modulation of both gonadotropin hormone and sex steroid levels. Prolonged activation of GnRHR results in significant downregulation of sex steroid levels, which is primarily responsible for the clinical efficacy of leuprolide in diverse conditions, including advanced prostate cancer, endometriosis, and central precocious puberty.[A203126, A203132] Leuprolide was first approved in 1985 as a daily subcutaneous injection under the tradename
Haloperidol is a high potency first-generation (typical) antipsychotic and one of the most frequently used antipsychotic medications used worldwide. While haloperidol has demonstrated pharmacologic activity at a number of receptors in the brain, it exerts its antipsychotic effect through its strong antagonism of the dopamine receptor (mainly D2), particularly within the mesolimbic and mesocortical systems of the brain. Haloperidol is indicated for the treatment of the manifestations of several psychotic disorders including schizophrenia, acute psychosis, Tourette syndrome, and other severe behavioural states. It is also used off-label for the management of chorea associated with Huntington's disease and for the treatment of intractable hiccups as it is a potent antiemetic. Dopamine-antagonizing medications such as haloperidol are though to improve psychotic symptoms and states that are caused by an over-production of dopamine, such as schizophrenia, which is theorized to be caused by a hyperdopaminergic state within the limbic system of the brain. Use of the first-generation antipsychotics (including haloperidol) is considered highly effective for the management of the "positive" symptoms of schizophrenia including hallucinations, hearing voices, aggression/hostility, disorganized speech, and psychomotor agitation. However, this class of drugs is also limited by the development of movement disorders induced by dopamine-blockade such as drug-induced parkinsonism, akathisia, dystonia, tardive dyskinesia, as well as other side effects including sedation, weight gain, and prolactin changes. While there are limited high-quality studies comparing haloperidol to lower-potency first-generation antipsychotics such as , , , and , haloperidol typically demonstrates the least amount of side effects within this class, but demonstrates a stronger disposition for causing extrapyramidal symptoms (EPS).[A180613, A180616, A180625] These other low‐potency antipsychotics are limited by their lower affinity for dopamine receptors, which requires a higher dose to effectively treat symptoms of schizophrenia. In addition, they block many receptors other than the primary target (dopamine receptors), such as cholinergic or histaminergic receptors, resulting in a higher incidence of side effects such as sedation, weight gain, and hypotension. Interestingly, in vivo pharmacogenetic studies have demonstrated that the metabolism of haloperidol may be modulated by genetically determined polymorphic _CYP2D6_ activity. However, these findings contradict the findings from studies in vitro with human liver microsomes and from drug interaction studies in vivo. Inter-ethnic and pharmacogenetic differences in haloperidol metabolism may possibly explain these observations. First-generation antipsychotic drugs have largely been replaced with second- and third-generation (atypical) antipsychotics such as , , , , , and . However, haloperidol use remains widespread and is considered the benchmark for comparison in trials of the newer generation antipsychotics. The efficacy of haloperidol was first established in controlled trials in the 1960s.
Haloperidol {u} (Compound) resembles {v} (Compound) Bepotastine
Haloperidol {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Loperamide
Haloperidol {u} (Compound) resembles {v} (Compound) Sertindole
Haloperidol {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Cetirizine
Haloperidol {u} (Compound) binds {v} (Gene) CYP2C9
Haloperidol {u} (Compound) palliates {v} (Disease) schizophrenia
Haloperidol {u} (Compound) downregulates {v} (Gene) CDC20
Haloperidol {u} (Compound) causes {v} (Side Effect) Extrapyramidal disorder
Haloperidol {u} may cause a minor interaction that can limit clinical effects when taken with {v} Metronidazole
Haloperidol {u} may lead to a major life threatening interaction when taken with {v} Anagrelide
Haloperidol (Compound) resembles Bepotastine (Compound)
Haloperidol may cause a moderate interaction that could exacerbate diseases when taken with Loperamide
Haloperidol (Compound) resembles Sertindole (Compound)
Haloperidol may cause a moderate interaction that could exacerbate diseases when taken with Cetirizine
Haloperidol (Compound) binds CYP2C9 (Gene)
Haloperidol (Compound) palliates schizophrenia (Disease)
Haloperidol (Compound) downregulates CDC20 (Gene)
Haloperidol (Compound) causes Extrapyramidal disorder (Side Effect)
Haloperidol may cause a minor interaction that can limit clinical effects when taken with Metronidazole
Haloperidol may lead to a major life threatening interaction when taken with Anagrelide