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The Annals of Pharmacotherapy Dec 1995To review the pharmacology, pharmacokinetics, clinical efficacy, and adverse effects of granisetron, focusing on critical analysis of published clinical trials and... (Review)
Review
OBJECTIVE
To review the pharmacology, pharmacokinetics, clinical efficacy, and adverse effects of granisetron, focusing on critical analysis of published clinical trials and comparison with other antiemetic agents, including ondansetron.
DATA SOURCES
MEDLINE (1966-1995) and CANCERLIT (1991-1995) searches of English-language literature using the terms "granisetron" and "granisetron (rn)" were performed.
STUDY SELECTION AND DATA EXTRACTION
All articles were considered for possible inclusion in this review. Abstracts of clinical trials were included only when they were judged to add critical information not otherwise available in the medical literature. For studies published more than once, the most recent publication was cited.
DATA SYNTHESIS
Nausea and vomiting are rated by patients as the most distressing chemotherapy-related adverse effects and may produce potentially life-threatening complications. The discovery of the role of serotonin in nausea and vomiting and the development of selective serotonin3-receptor (5-HT3) antagonists has significantly diminished the incidence and consequences of chemotherapy-related nausea and vomiting. Granisetron is the second 5-HT3-receptor antagonist to be marketed in the US. Granisetron has been compared with other antiemetic agents, including ondansetron, against highly and moderately emetogenic chemotherapy. The results of these trials have shown granisetron to be superior to conventional antiemetics and as effective as ondansetron in the prevention of chemotherapy-induced nausea and vomiting. The optimal dose of granisetron has yet to be determined. Formulary decisions should be based on a cost comparison among the 5-HT3-receptor antagonists at individual institutions.
CONCLUSIONS
Granisetron is a safe, effective antiemetic agent for the management of nausea and vomiting caused by cancer chemotherapy.
Topics: Antiemetics; Granisetron; Serotonin Antagonists
PubMed: 8672830
DOI: 10.1177/106002809502901211 -
Anesthesiology Clinics Jun 2014In a growing outpatient surgical population, postdischarge nausea and vomiting (PDNV) is unfortunately a common and costly anesthetic complication. Identification of... (Review)
Review
In a growing outpatient surgical population, postdischarge nausea and vomiting (PDNV) is unfortunately a common and costly anesthetic complication. Identification of risk factors for both postoperative nausea and vomiting and PDNV is the hallmark of prevention and management. New pharmacologic interventions with extended duration of action, including palonosetron and aprepritant, may prove to be more efficacious.
Topics: Antiemetics; Humans; Isoquinolines; Neurokinin-1 Receptor Antagonists; Palonosetron; Patient Discharge; Postoperative Nausea and Vomiting; Quinuclidines; Serotonin Antagonists; Time Factors
PubMed: 24882134
DOI: 10.1016/j.anclin.2014.02.004 -
Pharmacology, Biochemistry, and Behavior Apr 1984The effect of clozapine on the central serotonergic transmission system was studied by investigation of open-field motility of rats after microinjection of drugs into...
The effect of clozapine on the central serotonergic transmission system was studied by investigation of open-field motility of rats after microinjection of drugs into nucleus accumbens and median raphe nucleus. Previous work has shown that LSD in low doses potentiates apomorphine-induced hypermotility and that this LSD effect is induced by a serotonin agonist action in median raphe nucleus. Clozapine, injected into median raphe nucleus (0.05 micrograms), suppressed the LSD effect in the same manner as serotonin antagonists did. Since alpha-adrenergic drugs, injected into median raphe nucleus, caused locomotor stimulant effects, an alpha- adrenalytic action of clozapine was excluded. Clozapine, injected into nucleus accumbens (0.2 micrograms), increased apomorphine-induced hypermotility, whereas the dopamine antagonist haloperidol suppressed it. Our results suggest a serotonin antagonist action of clozapine.
Topics: Animals; Apomorphine; Clonidine; Clozapine; Dibenzazepines; Drug Interactions; Haloperidol; Lysergic Acid Diethylamide; Male; Microinjections; Motor Activity; Nucleus Accumbens; Phentolamine; Raphe Nuclei; Rats; Rats, Inbred Strains; Serotonin Antagonists
PubMed: 6728869
DOI: 10.1016/0091-3057(84)90297-1 -
American Journal of Hypertension Jul 1988Ketanserin is an agent whose main pharmacologic action is antagonism of serotonin (5-hydroxytryptamine, 5HT) receptors of the 5HT2 subtype. It also has weak alpha... (Comparative Study)
Comparative Study Review
Ketanserin is an agent whose main pharmacologic action is antagonism of serotonin (5-hydroxytryptamine, 5HT) receptors of the 5HT2 subtype. It also has weak alpha 1-adrenergic blocking properties, which may contribute to the acute blood pressure lowering effects seen in animal models of hypertension. During chronic treatment of hypertension in animals, the 5HT2 antagonistic properties, or a combination of 5HT2 and alpha 1-antagonistic effects, seems to be responsible for ketanserin's hypotensive action. Studies of patients with hypertension have demonstrated the therapeutic effects of ketanserin in monotherapy and combination therapy. In humans, the drug has a terminal half-life of 12-25 hours, and a twice daily dosage will lower blood pressure over the day. Ketanserin is a vasodilator that acts on both resistance and capacitance vessels. Chronic treatment with the drug causes minimal reflex changes in cardiovascular function, as well as sustained blood pressure reduction comparable with the effects of beta-adrenergic blockers or diuretics. In elderly patients, the therapeutic effects of ketanserin appear to be greater, and side effects are less frequent compared with beta-blockers and diuretics. In addition to its antihypertensive action, ketanserin also produces other effects that may be important in reducing cardiovascular morbidity and mortality in patients with hypertension. Some studies have shown a reduction in total and low-density lipoprotein (LDL) cholesterol, and a rise in high-density lipoprotein (HDL) cholesterol. Ketanserin also reduces ex vivo platelet aggregation and inhibits the serotonin-induced platelet release reaction. Worldwide experience with ketanserin in the treatment of hypertension indicates that it is a safe and effective agent for long-term therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Animals; Antihypertensive Agents; Cardiovascular Diseases; Cardiovascular System; Dose-Response Relationship, Drug; Humans; Hypertension; Ketanserin; Serotonin; Serotonin Antagonists
PubMed: 3046635
DOI: 10.1093/ajh/1.3.317s -
Expert Opinion on Pharmacotherapy Apr 2019Agomelatine is an antidepressant with unique pharmacological actions; it is both a melatonin agonist and selective serotonin antagonist. Both actions combined are... (Review)
Review
Agomelatine is an antidepressant with unique pharmacological actions; it is both a melatonin agonist and selective serotonin antagonist. Both actions combined are necessary for antidepressant efficacy. Effects on melatonin receptors enable resynchronisation of disrupted circadian rhythms with beneficial effects on sleep patterns. Areas covered: The issue of use of an antidepressant for depression co-morbid with somatic disorders is covered by the authors. A review of the literature from 2000 to August 2018 was undertaken using Scopus and Web of Science with the key words: agomelatine, depression, medical illness. Depression in Parkinson's disease, cardiovascular illness and type II diabetes is reviewed with evidence of efficacy. Bipolar depression and seasonal affective disorder may also react favourably. Agomelatine may have specific efficacy on symptoms of anhedonia. Expert opinion: Despite approval in some major jurisdictions, the drug has failed to gain registration in the United States. A defining issue may be questions about longer term efficacy: unequivocal effectiveness in placebo-controlled relapse prevention studies has not always been demonstrated. Continuation studies suggest maintenance of clinical responsiveness. A major disadvantage of the drug is its' potential hepatotoxicity and the need for repeated clinical laboratory tests.
Topics: Acetamides; Antidepressive Agents; Bipolar Disorder; Circadian Rhythm; Depression; Diabetes Mellitus, Type 2; Humans; Hypnotics and Sedatives; Seasonal Affective Disorder; Serotonin Antagonists
PubMed: 30759026
DOI: 10.1080/14656566.2019.1574747 -
Progress in Drug Research. Fortschritte... 1993Structural variations from agonists to their selective antagonists seemed to follow certain patterns. To analyze the variation patterns in the structural modification... (Review)
Review
Structural variations from agonists to their selective antagonists seemed to follow certain patterns. To analyze the variation patterns in the structural modification processes in past examples as well as to utilize the "common" variation patterns as possible principles to design new selective antagonistic drugs, the structures of agonists and their antagonists were superimposed on a two-dimensional grid template composed of regular hexagons and the topological similarities and dissimilarities of substructural elements between agonists and antagonists were examined. Between several pairs of neurotransmitter amines and their "selective" antagonists, similar patterns were disclosed in their structural modification processes. The generalized structural modification patterns were successfully applied as guiding principles to design and identify a new prototype structure of the 5-HT3 antagonist. The prototype structure was optimized by use of QSAR procedures leading to a compound which shows a potent antiemetic activity as well as a powerful gastrointestinal-motility modulation.
Topics: Animals; Drug Design; Humans; Receptors, Neurotransmitter; Serotonin Antagonists; Structure-Activity Relationship
PubMed: 8108562
DOI: 10.1007/978-3-0348-7150-1_10 -
Important Advances in Oncology 1994
Comparative Study Review
Topics: Administration, Oral; Adult; Antineoplastic Agents; Child; Cisplatin; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Dexamethasone; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Humans; Injections, Intravenous; Metoclopramide; Nausea; Ondansetron; Randomized Controlled Trials as Topic; Receptors, Serotonin; Serotonin; Serotonin Antagonists; Vomiting
PubMed: 8206488
DOI: No ID Found -
Journal of Biomolecular Screening Jun 2002Characterization of the potencies of agonists and antagonists in cell-based assays can be complicated by nonequilibrium conditions of functional response. We assessed...
Serotonin antagonist profiling on 5HT2A and 5HT2C receptors by nonequilibrium intracellular calcium response using an automated flow-through fluorescence analysis system, HT-PS 100.
Characterization of the potencies of agonists and antagonists in cell-based assays can be complicated by nonequilibrium conditions of functional response. We assessed the potencies of a series of serotonin (5HT) antagonists by inhibition of intracellular calcium response in HEK 293 cells expressing 5HT(2A) or 5HT(2C) receptors. An automated system, HT-PS 100, was used to profile the antagonists in two experimental setups: coadministration of agonist and antagonist to cells and preincubation of the cells with antagonist prior to agonist administration. We showed that the antagonist potencies (pIC(50) values) determined in the preincubation configuration were close to or exceeded those measured in the coadministration configuration. Closeness of the potencies determined in the two configurations supposedly reflected a rapid antagonist-receptor equilibration, whereas a significantly higher preincubation potency implied slow antagonist dissociation from the receptor. Schild analysis of the inhibition of serotonin-induced cell response by a competitive 5HT(2A) antagonist, spiperone, showed a typical competitive inhibition pattern when both the agonist and antagonist were applied simultaneously. Contrary to this, an insurmountable diminishing of the maximal cell response to serotonin was observed when the cells were preincubated with spiperone. We conclude that a combination of the coadministration and preincubation experimental setups is necessary for appropriate mechanistic interpretation and quantitative assessment of the antagonist activity when using transient functional readouts.
Topics: Calcium; Fluorescence; Humans; Receptors, Serotonin; Serotonin Antagonists; Spiperone
PubMed: 12097192
DOI: 10.1177/108705710200700313 -
Lancet (London, England) Oct 1982
Topics: Cardiovascular System; Humans; Hypertension; Ketanserin; Piperidines; Receptors, Serotonin; Serotonin; Serotonin Antagonists
PubMed: 6126719
DOI: No ID Found -
Cardiovascular Drugs and Therapy Jan 1990In this survey the possible role of serotonin in such acute disorders as systemic and pulmonary hypertension following cardiac surgery is discussed. Although platelets... (Review)
Review
In this survey the possible role of serotonin in such acute disorders as systemic and pulmonary hypertension following cardiac surgery is discussed. Although platelets are activated during cardiopulmonary bypass, the increase in serotonin plasma levels is limited because the serotonin released is taken up by normal platelets and endothelial cells. This does not imply that serotonin is not involved in the origin of systemic hypertension during and after cardiac surgery, because subthreshold or threshold doses of this amine amplify the vasoconstrictive effect of, for example, epinephrine and norepinephrine, the levels of which are significantly elevated under these circumstances. That serotonin plays a role through its amplifying effect is supported by the finding that ketanserin, a specific S2-serotonergic receptor antagonist with alpha 1-adrenergic receptor blocking properties, effectively lowers arterial blood pressure in patients with systemic postoperative hypertension by combined blockade of these receptors. The compound is also effective in the treatment of pulmonary hypertension after valve replacement, indicating that serotonin plays a role in the origin of this disorder. This idea is supported by the experimental finding that serotonin induces pulmonary hypertension. It is an interesting observation that, unlike such compounds as nitroprusside, ketanserin does not affect intrapulmonary shunting in patients with systemic hypertension and even reduces the intrapulmonary shunt fraction in patients with pulmonary hypertension. These findings indicate that this compound dilates the resistance vessels in well-ventilated, but not in poorly ventilated areas, and may dilate constricted bronchi.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Acute Disease; Animals; Cardiovascular Diseases; Humans; Serotonin; Serotonin Antagonists
PubMed: 2285646
DOI: 10.1007/BF00053422