The Experts below are selected from a list of 90 Experts worldwide ranked by ideXlab platform

Nissar A Darmani - One of the best experts on this subject based on the ideXlab platform.

  • receptor mechanism and antiemetic activity of structurally diverse cannabinoids against Radiation Induced Emesis in the least shrew
    European Journal of Pharmacology, 2007
    Co-Authors: Nissar A Darmani, Jano J Janoyan, Jennifer L Crim, Juan Ramírez
    Abstract:

    Xenobiotic cannabinoid CB1/CB2-receptor agonists appear to possess broad-spectrum antiemetic activity since they prevent vomiting produced by a variety of emetic stimuli including the chemotherapeutic agent cisplatin, serotonin 5-HT3-receptor agonists, dopamine D2/D3-receptor agonists and morphine, via the stimulation of CB1-receptors. The purpose of this study was to evaluate whether structurally diverse cannabinoids [Δ 9 -THC, (delta -9- tetrahydrocannabinol); (Δ 8 THC, delta -8-etrahydrocannabinol); WIN55,212-2, (R (+)-[2,3-dihydro-5-methyl-3[(morpholinyl)), methyl] pyrolol [1, 2, 3 – de] – 1, 4 benzoxazinyl] – (1-naphthalenyl) methenone mesylate); and CP55,940, ((-) - 3- [2-hydroxy-4- (1,1 - dimethylheptyl] - 4 – [3 – hydroxypropyl] cyclohexan –1 – ol)), can prevent Radiation-Induced Emesis. Exposure to total body Radiation (0, 5, 7.5 and 10 Gy) caused robust Emesis in the least shrew (Cryptotis parva) in a dose-dependent manner (ED50= 5.99 (5.77 – 6.23) Gy) and all animals vomited at the highest tested dose of Radiation. In addition, the Radiation exposure reduced locomotor behaviors to a significant but mild degree in a non-dose-dependent fashion up to one hour posttreatment. Radiation-Induced Emesis (10 Gy) was blocked in a dose-dependent manner by the CB1/CB2– receptor agonists with the following ID50potency order: CP55,940 (0.11 (0.09 - 0.12) mg/kg) > WIN55, 212,2 (3.65 (3.15 – 4.23) mg/ kg) = Δ 8 -THC (4.36 (3.05 – 6.22) mg/kg) > Δ 9 -THC (6.76 (5.22 – 8.75) mg/kg). Although the greater antiemetic potency and efficacy of Δ 8 -THC relative to its isomer Δ 9 -THC is unusual as the latter cannabinoid possesses higher affinity and potency for cannabinoid receptors in functional assays, the current data support the results of a clinical study in children suggestive of complete protection from Emesis by Δ 8 -THC. This effect has not been clinically observed for Δ 9 -THC in cancer patients receiving chemo- or Radiation-therapy.Cannabinoids prevented the Induced Emesis via the stimulation of cannabinoid CB1- receptors because the CB1(SR141716A) – and not the CB2(SR144528) –receptor antagonist reversed both the observed reduction in Emesis frequency and shrew Emesis protection afforded by either Δ 9 -THC or CP55,940 against Radiation-Induced Emesis. These findings further suggest that the least shrew can be utilized as a versatile and inexpensive small animal model to rapidly screen the efficacy of investigational antiemetics for the prevention of Radiation-Induced Emesis.

  • receptor mechanism and antiemetic activity of structurally diverse cannabinoids against Radiation Induced Emesis in the least shrew
    European Journal of Pharmacology, 2007
    Co-Authors: Nissar A Darmani, Jano J Janoyan, Jennifer L Crim, Juan R Ramirez
    Abstract:

    Xenobiotic cannabinoid CB1/CB2-receptor agonists appear to possess broad-spectrum antiemetic activity since they prevent vomiting produced by a variety of emetic stimuli including the chemotherapeutic agent cisplatin, serotonin 5-HT3-receptor agonists, dopamine D2/D3-receptor agonists and morphine, via the stimulation of CB1-receptors. The purpose of this study was to evaluate whether structurally-diverse cannabinoids [Delta9-THC, (delta-9-tetrahydrocannabinol); (Delta8-THC, delta-8-tetrahydrocannabinol); WIN55,212-2, (R (+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)), methyl] pyrolol [1,2,3-de]-1,4 benzoxazinyl]-(1-naphthalenyl) methenone mesylate); and CP55,940, ((-)-3-[2-hydroxy-4-(1,1-dimethylheptyl]-4-[3-hydroxypropyl] cyclohexane-1-ol)), can prevent Radiation-Induced Emesis. Exposure to total body Radiation (0, 5, 7.5 and 10 Gy) caused robust Emesis in the least shrew (Cryptotis parva) in a dose-dependent manner (ED50=5.99 (5.77-6.23) Gy) and all animals vomited at the highest tested dose of Radiation. In addition, the Radiation exposure reduced locomotor behaviors to a significant but mild degree in a non-dose-dependent fashion up to one hour post-treatment. Radiation-Induced Emesis (10 Gy) was blocked in a dose-dependent manner by the CB1/CB2-receptor agonists with the following ID50 potency order: CP55,940 (0.11 (0.09-0.12) mg/kg)>WIN55,212,2 (3.65 (3.15-4.23) mg/kg)=Delta8-THC (4.36 (3.05-6.22) mg/kg)>Delta9-THC (6.76 (5.22-8.75) mg/kg). Although the greater antiemetic potency and efficacy of Delta8-THC relative to its isomer Delta9-THC is unusual as the latter cannabinoid possesses higher affinity and potency for cannabinoid receptors in functional assays, the current data support the results of a clinical study in children suggestive of complete protection from Emesis by Delta8-THC. This effect has not been clinically observed for Delta9-THC in cancer patients receiving chemo- or Radiation-therapy. Cannabinoids prevented the Induced Emesis via the stimulation of cannabinoid CB1-receptors because the CB1 (SR141716A)--and not the CB2 (SR144528)--receptor antagonist reversed both the observed reduction in Emesis frequency and shrew Emesis protection afforded by either Delta9-THC or CP55,940 against Radiation-Induced Emesis. These findings further suggest that the least shrew can be utilized as a versatile and inexpensive small animal model to rapidly screen the efficacy of investigational antiemetics for the prevention of Radiation-Induced Emesis.

Roger F Anderson - One of the best experts on this subject based on the ideXlab platform.

  • on the mechanism of Radiation Induced Emesis the role of serotonin
    International Journal of Radiation Oncology Biology Physics, 1993
    Co-Authors: Charles W Scarantino, Robert D Ornitz, Leroy G Hoffman, Roger F Anderson
    Abstract:

    Abstract Purpose : The aim of this study was to determine the mechanism of action of Radiation-Induced Emesis by determining the incidence of Radiation-Induced Emesis following hemibody irRadiation; the effects of specific antiemetics especially ondansetron, a 5-hydroxytryptamine receptor antagonist, and to determine the relationship between Radiation-Induced Emesis and serotonin (5-hydroxytryptamine) through its active metabolite, 5-hydroxyindoleacetic acid (5-HIAA). Methods and Materials : Forty-one patients received 53 hemibody treatments of 5–8 Gy following intravenous hydration. The patients were divided into three groups according to prehemibody irrRadiation treatment: Group A: no pretreatment antiemetics, 30 patients; Group B: nonondansetron antiemetics (metoclopramide, dexamethasone, prochlorperazine), ten patients; and Group C: ondansetron, 13 patients. The incidence of Radiation-Induced Emesis was determined prehemibody irRadiation or baseline and at 1 h posthemibody irRadiation in 38 patients and the results expressed as the percent change in 5-HIAA (ng/ug creatinine). Results: The incidence of Radiation-Induced Emesis was 82% ( 14 17 ) following upper/mid hemibody irRadiation and 15% ( 2 11 ) following lower hemibody irRadiation in Group A; 50% ( 3 6 ) and 25% ( 1 4 ) following upper/mid and lower hemibody irRadiation respectively, in Group B; and 0% ( 0 13 ) after upper/mid hemibody irRadiation in Group C. The incidence of Emesis was significantly different (p Conclusion: The higher incidence of Radiation-Induced Emesis following upper and mid hemibody irRadiation in antiemetic naive patients compared to the incidence following lower hemibody irRadiation suggests that the critical organ responsible for Radiation sickness is in the abdomen. The control of Emesis by ondansetron, a 5-HT3 receptor antagonist, attests to the efficacy of ondansetron in Radiation-Induced Emesis and suggests a role for serotonin in mediating Radiation-Induced Emesis. Finally, the parallel changes in 5-HIAA and the incidence of Emesis provides additional evidence for a more direct role for serotonin in Radiation-Induced Emesis.

  • Radiation Induced Emesis effects of ondansetron
    Seminars in Oncology, 1992
    Co-Authors: Charles W Scarantino, Robert D Ornitz, Leroy G Hoffman, Roger F Anderson
    Abstract:

    The incidence, severity, and onset of Radiation-Induced Emesis (RIE) are related to field size, site, and dose per fraction. Radiation-Induced Emesis can occur (1) within 2 to 3 weeks in approximately 50% of patients after conventional fractionated radiotherapy (200 cGy/fraction) to the upper abdomen, (2) acutely in more than 90% of patients receiving fractionated total body irRadiation (TBI) for bone marrow transplantation, and (3) within 30 to 60 minutes in more than 80% of patients following single high-dose (> 500 cGy)/large field hemibody irRadiation (HBI). The increased frequency of Emesis associated with TBI and HBI has renewed the interest in the mechanism and treatment of RIE. A number of studies have reported a significant difference in the incidence of Emesis following doses of > or = 500 cGy to the upper-mid (> 80%) and lower (20% to 40%) hemibody. The data suggested that the organ responsible for emetic response was in the upper abdomen. However, the mechanism of RIE is not well understood, although degradation products from normal tissues and tumor have been suggested. The introduction and effectiveness of the 5-hydroxytryptamine3 receptor antagonists in chemotherapy-Induced Emesis and the location of these receptors in the upper abdomen (possible site of the Radiation-associated emetic response) suggested that this group of compounds may have a role in RIE. Lucraft and Palmer (Clin Radiol 33:621-622, 1982) reported no differences between levonantradol and chlorpromazine in preventing RIE in patients treated with single doses of more than 10 Gy to a small upper abdominal field. Priestman (Eur J Cancer Clin Oncol 25:529-533, 1989 [Suppl]) reported on a pilot and randomized study with ondansetron after single doses of 8 to 10 Gy to the upper abdomen. In the pilot study, ondansetron achieved major or complete control of vomiting in 77% to 90% of patients; subsequently, he reported a significant difference between ondansetron (97%) and metoclopramide (45%) in controlling RIE on the day of radiotherapy. Hewitt et al (Bone Marrow Transpl 7:431-433, 1991) reported a complete or major response on 93% of the days of ondansetron therapy during pretreatment therapy with cyclophosphamide and TBI for bone marrow transplantation. A preliminary analysis of 41 patients treated with HBI at the Rex Cancer Center confirms the role of ondansetron in RIE. Twenty-eight patients (upper-mid 16 patients/lower HBI 12 patients) did not receive pretreatment antiemetics (group A); seven received non-ondansetron pre-HBI (group B); and six received ondansetron (group C).(ABSTRACT TRUNCATED AT 400 WORDS)

Juan R Ramirez - One of the best experts on this subject based on the ideXlab platform.

  • receptor mechanism and antiemetic activity of structurally diverse cannabinoids against Radiation Induced Emesis in the least shrew
    European Journal of Pharmacology, 2007
    Co-Authors: Nissar A Darmani, Jano J Janoyan, Jennifer L Crim, Juan R Ramirez
    Abstract:

    Xenobiotic cannabinoid CB1/CB2-receptor agonists appear to possess broad-spectrum antiemetic activity since they prevent vomiting produced by a variety of emetic stimuli including the chemotherapeutic agent cisplatin, serotonin 5-HT3-receptor agonists, dopamine D2/D3-receptor agonists and morphine, via the stimulation of CB1-receptors. The purpose of this study was to evaluate whether structurally-diverse cannabinoids [Delta9-THC, (delta-9-tetrahydrocannabinol); (Delta8-THC, delta-8-tetrahydrocannabinol); WIN55,212-2, (R (+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)), methyl] pyrolol [1,2,3-de]-1,4 benzoxazinyl]-(1-naphthalenyl) methenone mesylate); and CP55,940, ((-)-3-[2-hydroxy-4-(1,1-dimethylheptyl]-4-[3-hydroxypropyl] cyclohexane-1-ol)), can prevent Radiation-Induced Emesis. Exposure to total body Radiation (0, 5, 7.5 and 10 Gy) caused robust Emesis in the least shrew (Cryptotis parva) in a dose-dependent manner (ED50=5.99 (5.77-6.23) Gy) and all animals vomited at the highest tested dose of Radiation. In addition, the Radiation exposure reduced locomotor behaviors to a significant but mild degree in a non-dose-dependent fashion up to one hour post-treatment. Radiation-Induced Emesis (10 Gy) was blocked in a dose-dependent manner by the CB1/CB2-receptor agonists with the following ID50 potency order: CP55,940 (0.11 (0.09-0.12) mg/kg)>WIN55,212,2 (3.65 (3.15-4.23) mg/kg)=Delta8-THC (4.36 (3.05-6.22) mg/kg)>Delta9-THC (6.76 (5.22-8.75) mg/kg). Although the greater antiemetic potency and efficacy of Delta8-THC relative to its isomer Delta9-THC is unusual as the latter cannabinoid possesses higher affinity and potency for cannabinoid receptors in functional assays, the current data support the results of a clinical study in children suggestive of complete protection from Emesis by Delta8-THC. This effect has not been clinically observed for Delta9-THC in cancer patients receiving chemo- or Radiation-therapy. Cannabinoids prevented the Induced Emesis via the stimulation of cannabinoid CB1-receptors because the CB1 (SR141716A)--and not the CB2 (SR144528)--receptor antagonist reversed both the observed reduction in Emesis frequency and shrew Emesis protection afforded by either Delta9-THC or CP55,940 against Radiation-Induced Emesis. These findings further suggest that the least shrew can be utilized as a versatile and inexpensive small animal model to rapidly screen the efficacy of investigational antiemetics for the prevention of Radiation-Induced Emesis.

Juan Ramírez - One of the best experts on this subject based on the ideXlab platform.

  • receptor mechanism and antiemetic activity of structurally diverse cannabinoids against Radiation Induced Emesis in the least shrew
    European Journal of Pharmacology, 2007
    Co-Authors: Nissar A Darmani, Jano J Janoyan, Jennifer L Crim, Juan Ramírez
    Abstract:

    Xenobiotic cannabinoid CB1/CB2-receptor agonists appear to possess broad-spectrum antiemetic activity since they prevent vomiting produced by a variety of emetic stimuli including the chemotherapeutic agent cisplatin, serotonin 5-HT3-receptor agonists, dopamine D2/D3-receptor agonists and morphine, via the stimulation of CB1-receptors. The purpose of this study was to evaluate whether structurally diverse cannabinoids [Δ 9 -THC, (delta -9- tetrahydrocannabinol); (Δ 8 THC, delta -8-etrahydrocannabinol); WIN55,212-2, (R (+)-[2,3-dihydro-5-methyl-3[(morpholinyl)), methyl] pyrolol [1, 2, 3 – de] – 1, 4 benzoxazinyl] – (1-naphthalenyl) methenone mesylate); and CP55,940, ((-) - 3- [2-hydroxy-4- (1,1 - dimethylheptyl] - 4 – [3 – hydroxypropyl] cyclohexan –1 – ol)), can prevent Radiation-Induced Emesis. Exposure to total body Radiation (0, 5, 7.5 and 10 Gy) caused robust Emesis in the least shrew (Cryptotis parva) in a dose-dependent manner (ED50= 5.99 (5.77 – 6.23) Gy) and all animals vomited at the highest tested dose of Radiation. In addition, the Radiation exposure reduced locomotor behaviors to a significant but mild degree in a non-dose-dependent fashion up to one hour posttreatment. Radiation-Induced Emesis (10 Gy) was blocked in a dose-dependent manner by the CB1/CB2– receptor agonists with the following ID50potency order: CP55,940 (0.11 (0.09 - 0.12) mg/kg) > WIN55, 212,2 (3.65 (3.15 – 4.23) mg/ kg) = Δ 8 -THC (4.36 (3.05 – 6.22) mg/kg) > Δ 9 -THC (6.76 (5.22 – 8.75) mg/kg). Although the greater antiemetic potency and efficacy of Δ 8 -THC relative to its isomer Δ 9 -THC is unusual as the latter cannabinoid possesses higher affinity and potency for cannabinoid receptors in functional assays, the current data support the results of a clinical study in children suggestive of complete protection from Emesis by Δ 8 -THC. This effect has not been clinically observed for Δ 9 -THC in cancer patients receiving chemo- or Radiation-therapy.Cannabinoids prevented the Induced Emesis via the stimulation of cannabinoid CB1- receptors because the CB1(SR141716A) – and not the CB2(SR144528) –receptor antagonist reversed both the observed reduction in Emesis frequency and shrew Emesis protection afforded by either Δ 9 -THC or CP55,940 against Radiation-Induced Emesis. These findings further suggest that the least shrew can be utilized as a versatile and inexpensive small animal model to rapidly screen the efficacy of investigational antiemetics for the prevention of Radiation-Induced Emesis.

Jano J Janoyan - One of the best experts on this subject based on the ideXlab platform.

  • receptor mechanism and antiemetic activity of structurally diverse cannabinoids against Radiation Induced Emesis in the least shrew
    European Journal of Pharmacology, 2007
    Co-Authors: Nissar A Darmani, Jano J Janoyan, Jennifer L Crim, Juan Ramírez
    Abstract:

    Xenobiotic cannabinoid CB1/CB2-receptor agonists appear to possess broad-spectrum antiemetic activity since they prevent vomiting produced by a variety of emetic stimuli including the chemotherapeutic agent cisplatin, serotonin 5-HT3-receptor agonists, dopamine D2/D3-receptor agonists and morphine, via the stimulation of CB1-receptors. The purpose of this study was to evaluate whether structurally diverse cannabinoids [Δ 9 -THC, (delta -9- tetrahydrocannabinol); (Δ 8 THC, delta -8-etrahydrocannabinol); WIN55,212-2, (R (+)-[2,3-dihydro-5-methyl-3[(morpholinyl)), methyl] pyrolol [1, 2, 3 – de] – 1, 4 benzoxazinyl] – (1-naphthalenyl) methenone mesylate); and CP55,940, ((-) - 3- [2-hydroxy-4- (1,1 - dimethylheptyl] - 4 – [3 – hydroxypropyl] cyclohexan –1 – ol)), can prevent Radiation-Induced Emesis. Exposure to total body Radiation (0, 5, 7.5 and 10 Gy) caused robust Emesis in the least shrew (Cryptotis parva) in a dose-dependent manner (ED50= 5.99 (5.77 – 6.23) Gy) and all animals vomited at the highest tested dose of Radiation. In addition, the Radiation exposure reduced locomotor behaviors to a significant but mild degree in a non-dose-dependent fashion up to one hour posttreatment. Radiation-Induced Emesis (10 Gy) was blocked in a dose-dependent manner by the CB1/CB2– receptor agonists with the following ID50potency order: CP55,940 (0.11 (0.09 - 0.12) mg/kg) > WIN55, 212,2 (3.65 (3.15 – 4.23) mg/ kg) = Δ 8 -THC (4.36 (3.05 – 6.22) mg/kg) > Δ 9 -THC (6.76 (5.22 – 8.75) mg/kg). Although the greater antiemetic potency and efficacy of Δ 8 -THC relative to its isomer Δ 9 -THC is unusual as the latter cannabinoid possesses higher affinity and potency for cannabinoid receptors in functional assays, the current data support the results of a clinical study in children suggestive of complete protection from Emesis by Δ 8 -THC. This effect has not been clinically observed for Δ 9 -THC in cancer patients receiving chemo- or Radiation-therapy.Cannabinoids prevented the Induced Emesis via the stimulation of cannabinoid CB1- receptors because the CB1(SR141716A) – and not the CB2(SR144528) –receptor antagonist reversed both the observed reduction in Emesis frequency and shrew Emesis protection afforded by either Δ 9 -THC or CP55,940 against Radiation-Induced Emesis. These findings further suggest that the least shrew can be utilized as a versatile and inexpensive small animal model to rapidly screen the efficacy of investigational antiemetics for the prevention of Radiation-Induced Emesis.

  • receptor mechanism and antiemetic activity of structurally diverse cannabinoids against Radiation Induced Emesis in the least shrew
    European Journal of Pharmacology, 2007
    Co-Authors: Nissar A Darmani, Jano J Janoyan, Jennifer L Crim, Juan R Ramirez
    Abstract:

    Xenobiotic cannabinoid CB1/CB2-receptor agonists appear to possess broad-spectrum antiemetic activity since they prevent vomiting produced by a variety of emetic stimuli including the chemotherapeutic agent cisplatin, serotonin 5-HT3-receptor agonists, dopamine D2/D3-receptor agonists and morphine, via the stimulation of CB1-receptors. The purpose of this study was to evaluate whether structurally-diverse cannabinoids [Delta9-THC, (delta-9-tetrahydrocannabinol); (Delta8-THC, delta-8-tetrahydrocannabinol); WIN55,212-2, (R (+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)), methyl] pyrolol [1,2,3-de]-1,4 benzoxazinyl]-(1-naphthalenyl) methenone mesylate); and CP55,940, ((-)-3-[2-hydroxy-4-(1,1-dimethylheptyl]-4-[3-hydroxypropyl] cyclohexane-1-ol)), can prevent Radiation-Induced Emesis. Exposure to total body Radiation (0, 5, 7.5 and 10 Gy) caused robust Emesis in the least shrew (Cryptotis parva) in a dose-dependent manner (ED50=5.99 (5.77-6.23) Gy) and all animals vomited at the highest tested dose of Radiation. In addition, the Radiation exposure reduced locomotor behaviors to a significant but mild degree in a non-dose-dependent fashion up to one hour post-treatment. Radiation-Induced Emesis (10 Gy) was blocked in a dose-dependent manner by the CB1/CB2-receptor agonists with the following ID50 potency order: CP55,940 (0.11 (0.09-0.12) mg/kg)>WIN55,212,2 (3.65 (3.15-4.23) mg/kg)=Delta8-THC (4.36 (3.05-6.22) mg/kg)>Delta9-THC (6.76 (5.22-8.75) mg/kg). Although the greater antiemetic potency and efficacy of Delta8-THC relative to its isomer Delta9-THC is unusual as the latter cannabinoid possesses higher affinity and potency for cannabinoid receptors in functional assays, the current data support the results of a clinical study in children suggestive of complete protection from Emesis by Delta8-THC. This effect has not been clinically observed for Delta9-THC in cancer patients receiving chemo- or Radiation-therapy. Cannabinoids prevented the Induced Emesis via the stimulation of cannabinoid CB1-receptors because the CB1 (SR141716A)--and not the CB2 (SR144528)--receptor antagonist reversed both the observed reduction in Emesis frequency and shrew Emesis protection afforded by either Delta9-THC or CP55,940 against Radiation-Induced Emesis. These findings further suggest that the least shrew can be utilized as a versatile and inexpensive small animal model to rapidly screen the efficacy of investigational antiemetics for the prevention of Radiation-Induced Emesis.