Regional and functional differences of 5-hydroxytryptamine-receptor subtypes in guinea pig stomach.
Functions and the presence of 5-hydroxytryptamine (5-HT) receptors in the fundus, corpus and antrum of the guinea pig stomach were examined by measuring contractile force and acetylcholine (ACh) release. Stimulation of the 5-HT1 receptor caused tetrodotoxin (TTX)-insensitive relaxations in the preparations from 3 regions. Stimulation of the 5-HT2 receptor caused TTX-insensitive contractions in the preparations of fundus and antrum. Stimulation of 5-HT3 receptors caused contractions that were sensitive to TTX and atropine and enhanced the outflow of [3H]ACh from preparations of only antrum. Stimulation of 5-HT4 receptors caused contractions of antral strips and decreased relaxations of corporal strips and enhanced the outflow of [3H]ACh from the preparations of both corpus and antrum. In the guinea pig stomach, the fundus possesses relaxant 5-HT1 receptor < contractile 5-HT2 receptors and caused the contractile response to 5-HT. The corpus possesses relaxant 5-HT1 receptors and relaxant receptors other than 5-HT1, 5-HT2, 5-HT3 and 5-HT4 receptors > contractile 5-HT4 receptor, and therefore 5-HT caused relaxations. The antrum possesses relaxant 5-HT1 receptor < contractile 5-HT2, 5-HT3 and 5-HT4 receptors, and thus 5-HT caused contractions. (+info)
Antiemetic efficacy of granisetron plus dexamethasone in bone marrow transplant patients receiving chemotherapy and total body irradiation.
Few trials exist regarding the antiemetic efficacy of granisetron in bone marrow transplant (BMT) recipients conditioned with high-dose chemotherapy and total body irradiation (TBI). In this single-center, open-label, prospective, trial, the antiemetic efficacy and safety of granisetron plus dexamethasone were evaluated in 26 patients conditioned with cyclophosphamide-containing regimens (the majority receiving 60 mg/kg per day on 2 consecutive days), and TBI (12 Gy divided over 4 days). Daily intravenous doses of granisetron 1 mg plus dexamethasone 10 mg were given 30 min prior to chemotherapy or radiation, and continued for 24 h after the last conditioning treatment for a median of 6 days (range 3-9). Emetic control was defined by the number of emetic episodes occurring within a 24 h period, or the requirement for rescue medication for nausea or vomiting. A total of 25 patients completed 186 evaluable treatment days. Response (emetic control by treatment days) was complete in 50% of patients, major in 48%, minor in 2%, and there were no failures. Adverse effects were minor, with diarrhea (15%), headache (14%), and constipation (11%) reported most often. Based on these results, the antiemetic regimen of granisetron plus dexamethasone appears effective and well tolerated during BMT conditioning with high-dose cyclophosphamide and TBI. (+info)
Antiemetic efficacy of granisetron: a randomized crossover study in patients receiving cisplatin-containing intraarterial chemotherapy.
BACKGROUND: Cisplatin (CDDP) is one of the most active chemotherapeutic agents but is among the most emetogenic drugs. The emetic side-effects of CDDP-containing intraarterial chemotherapy have not been evaluated in a prospective randomized trial and the efficacy of serotonin antagonists in preventing the emesis associated with this method of CDDP administration has not been assessed. METHODS: CDDP 50 mg/m2 and methotrexate 30 mg/m2 were administered every 3 weeks through intraarterial catheters placed in the bilateral internal iliac arteries. Patients were classified into two groups: granisetron treatment group (group G) and no treatment group (group NG) with the first course of chemotherapy, crossing over with the second course. The patients in group G received granisetron 40 micrograms/kg by intravenous infusion. RESULTS: Although intraarterial CDDP administration produced less emesis than intravenous CDDP administration, at the same concentration, gastrointestinal toxicity is still the most unpleasant side-effect for patients. Granisetron administration significantly reduced nausea and vomiting during the acute emetic phase (an evaluation of treatment as very effective and effective was made in 89% in group G and 33% in group NG (P < 0.001). Complete control of emesis was achieved in 68 and 18% of patients in groups G and NG, respectively (P < 0.0001). CONCLUSION: A single prophylactic infusion of granisetron was effective in preventing the nausea and vomiting associated with intraarterial CDDP-containing therapy. (+info)
Prophylactic antiemetic therapy with a combination of granisetron and dexamethasone in patients undergoing middle ear surgery.
We have compared the efficacy of granisetron in combination with dexamethasone with each drug alone in the prevention of postoperative nausea and vomiting (PONV) after middle ear surgery. In a randomized, double-blind study, 120 patients (85 females) received granisetron 3 mg, dexamethasone 8 mg or granisetron 3 mg with dexamethasone 8 mg i.v. (n = 40 in each group), immediately before induction of anaesthesia. A standardized general anaesthetic technique was used. A complete response, defined as no PONV and no need for another rescue antiemetic during the first 3 h after anaesthesia, was recorded in 83%, 50% and 98% of patients who had received granisetron, dexamethasone and granisetron-dexamethasone, respectively. The corresponding incidences during the next 21 h after anaesthesia were 80%, 55% and 98% (P < 0.05; overall Fisher's exact probability test). In summary, prophylactic use of combined granisetron and dexamethasone was more effective than each antiemetic alone for the prevention of PONV after middle ear surgery. (+info)
Granisetron (Kytril) suppresses methotrexate-induced nausea and vomiting among patients with inflammatory arthritis and is superior to prochlorperazine (Stemetil).
OBJECTIVE: Methotrexate (MTX) is an increasingly popular anti-rheumatic drug with its usefulness limited by toxicity, most commonly gastrointestinal (GI). The aim of the study was to study the effectiveness of the 5-HT3 receptor antagonist granisetron (GR) in the therapy of MTX-induced nausea. METHODS: A single-blind 8 week pilot study with random allocation to either GR 1 mg or prochlorperazine (Stemetil; PCh) 10 mg was undertaken in 13 patients who were taking or had taken MTX for either rheumatoid arthritis (10) or psoriatic arthritis (3). RESULTS: One in six patients treated with PCh completed the 8 week study compared to 7/7 treated with GR. After switching of symptomatic patients, 11 completed the study on GR and median improvement was by two grades (P < 0.001) with a significantly better visual analogue scale score for patient satisfaction compared to PCh. CONCLUSION: Treatment with GR may be useful in establishing and maintaining some patients on MTX where GI toxicity would have precluded such therapy. (+info)
Granisetron compared with prednisolone plus metopimazine as anti-emetic prophylaxis during multiple cycles of moderately emetogenic chemotherapy.
This randomized, double-blind, double-dummy parallel study compared the anti-emetic efficacy and tolerability of the serotonin antagonist granisetron with prednisolone plus the dopamine D2 antagonist metopimazine during nine cycles of moderately emetogenic chemotherapy. Chemotherapy naive women with stage I or II breast cancer scheduled to intravenous cyclophosphamide, fluorouracil and methotrexate or cyclophosphamide, epirubicin and fluorouracil every 3 weeks were included. Patients received a single intravenous dose of granisetron 3 mg or a 3-day oral treatment with prednisolone 25 mg once a day plus metopimazine 30 mg four times a day. A total of 223 women were enrolled and 218 patients (97.8%) were evaluable for efficacy. Granisetron (n = 109) was superior to prednisolone plus metopimazine (n = 109) in the prophylaxis of acute nausea and vomiting during the first cycle of chemotherapy (P < 0.001) and prednisolone plus metopimazine was superior on days 2-5 (P = 0.002). Overall, granisetron was superior on days 1-5 (P = 0.009). The median number of cycles completed with granisetron was five (95% confidence interval 4-6) compared with two (95% confidence interval 2-2) for prednisolone plus metopimazine (P = 0.0019). Constipation and rash were reported more frequently with granisetron (P < 0.001 and P = 0.043 respectively) and palpitations more frequently with prednisolone plus metopimazine (P = 0.015). In conclusion, the number of cycles completed with granisetron was significantly higher than the number completed with prednisolone plus metopimazine, but the anti-emetic efficacy of both treatments declined during multiple cycles of moderately emetogenic chemotherapy. (+info)
Involvement of serotonin and calcium channels in the intestinal fluid secretion evoked by bile salt and cholera toxin.
1. The enteric nervous system (ENS) is activated when exposing the intestinal mucosa to cholera toxin or certain bile salts. Cholera toxin stimulates ENS, at least in part, by the release of 5-hydroxytryptamine (5-HT) from the enterochromaffin cells. Calcium channel blockers of the L-type markedly attenuate the fluid secretion and the luminal release of 5-HT caused by cholera toxin. 2. The objective of the present study was to elucidate if sodium deoxycholate activated ENS in a similar manner as cholera toxin. Furthermore, the effect of several calcium channel blockers was tested on the fluid secretion caused by cholera toxin or bile salt. 3. Sodium deoxycholate (4 mM) caused a release of 5-HT into the intestinal lumen, which was inhibited by calcium channel blockade. Granisetron, a 5-HT3 receptor blocker, partly inhibited the fluid secretion caused by bile salt. 4. The effects of nifedipine, felodipine, R-felodipine, H186/86 (t-butyl analogue of felodipine) on the fluid secretion caused by cholera toxin or sodium deoxycholate were studied. Both secretory states were markedly attenuated in a dose dependent manner by all calcium channel blockers tested regardless of their effects on arterial pressure. 5. It is concluded that both cholera toxin and bile salt activate ENS, at least in part, via a release of 5-HT from the enterochromaffin cells. The antisecretory effect calcium channel blockers is partly explained by an inhibition of this release of 5-HT. (+info)
Randomized phase II study of the neurokinin 1 receptor antagonist CJ-11,974 in the control of cisplatin-induced emesis.
PURPOSE: To determine the efficacy and safety of the neurokinin type 1 receptor antagonist CJ-11,974 for the control of high-dose cisplatin-induced emesis. PATIENTS AND METHODS: A double-blind, randomized, phase II design with a group sequential stopping rule was used in this study. Sixty-one patients with cancer who were receiving cisplatin at a dose of at least 100 mg/m2 for the first time were enrolled. All patients received granisetron 10 microg/kg and dexamethasone 20 mg intravenously 30 minutes before they were given cisplatin. Patients were randomly assigned to two groups: group 1 received CJ-11,974 100 mg, and group 2 received placebo orally 30 minutes before and 12 hours after cisplatin and then twice daily on days 2 through 5 after cisplatin. The primary end point was the percentage of patients who developed delayed emesis (emesis on the second to fifth days after cisplatin). RESULTS: Thirty patients were enrolled in group 1, and 31 patients were enrolled in group 2. Fifty-eight patients were assessable for efficacy. Complete control of emesis (expressed as the percentage of patients who had no emesis) was as follows: day 1, 85.7% (group 1) and 66.7% (group 2) (P = .090); days 2 through 5, 67.8% (group 1) and 36.6% (group 2) (P = .0425, adjusted); days 1 through 5, 64.3% (group 1) and 30% (group 2) (P = .009). Patients in group 1 experienced significantly less nausea than patients in group 2 on day 1 (P = .024). Treatment was well tolerated in both groups. CONCLUSION: We conclude from this exploratory phase II trial that CJ-11,974 is superior to placebo in controlling cisplatin-induced delayed emesis and may provide additive benefit in acute emesis and nausea control when combined with a 5-hydroxytryptamine-3 receptor antagonist and dexamethasone. Additional larger trials are indicated to confirm the clinical value of CJ-11,974. (+info)