The Experts below are selected from a list of 180 Experts worldwide ranked by ideXlab platform

P Ward - One of the best experts on this subject based on the ideXlab platform.

  • gr205171 a novel antagonist with high affinity for the tachykinin nk1 receptor and potent broad spectrum anti Emetic activity
    Regulatory Peptides, 1996
    Co-Authors: C.j. Gardner, D R Armour, D T Beattie, J D Gale, G J Kilpatrick, D J Twissell, A.b. Hawcock, P Ward
    Abstract:

    Abstract It has been demonstrated recently that antagonists of the tachykinin NK1 receptor, specifically CP-99,994 and GR203040, possess anti-Emetic activity in a range of species. To optimise this activity, a series of analogues based around the structure of GR203040 have been synthesised and their affinity at the human tachykinin NK1 receptor determined. In addition, the potency of these analogues to inhibit emesis induced in the ferret by whole-body X-irradiation has been examined. A range of substitutions at the C-1 position of the tetrazole moiety in GR203040 were explored in vitro and in vivo. The trifluoromethyl compound, GR205171, was the most potent antagonist with regard to the ability to inhibit emesis induced by X-irradiation. This compound was demonstrated to have a broad spectrum of anti-Emetic activity, inhibiting emesis in the ferret induced by cisplatin, cyclophosphamide, morphine, ipecacuanha and copper sulphate. Furthermore, emesis was also inhibited in the house-musk shrew, Suncus murinus, when induced by either motion or cisplatin, and in the dog when induced by ipecacuanha. GR205171 has the most potent anti-Emetic activity of any tachykinin NK1 receptor antagonist described to date. The compound is orally active in the ferret and dog, long-lasting, and warrants further investigation as a potential broad-spectrum anti-Emetic Agent.

  • the broad spectrum anti Emetic activity of the novel non peptide tachykinin nk1 receptor antagonist gr203040
    British Journal of Pharmacology, 1995
    Co-Authors: C.j. Gardner, J D Gale, G J Kilpatrick, D J Twissell, C.c. Jordan, Tim J Dale, Chas Bountra, P Ward
    Abstract:

    1. Following our earlier observations that the tachykinin NK1 receptor antagonist CP-99,994 is an effective anti-Emetic in ferrets, we have examined the anti-Emetic effects of a more potent and novel NK1 receptor antagonist, GR203040, against various Emetic stimuli in the ferret, dog and house musk shrew (Suncus murinus). 2. In ferrets, GR203040 (0.1 mg kg-1 s.c. or i.v.) is effective against emesis induced by radiation, cisplatin, cyclophosphamide, copper sulphate, ipecacuanha or morphine. 3. In animals in which emesis had been established with cisplatin, GR203040 (1 mg kg-1 s.c.) was fully effective as an interventional treatment. No further emesis was seen in animals treated with GR203040 whilst saline-treated animals continued to vomit. 4. GR203040 (0.1 mg kg-1 s.c.) retains anti-Emetic efficacy in the ferret, even when given as a 6 h pretreatment, indicating that this compound has a long duration of action. The compound is also effective orally at the same dose, when given as a 90 min pretreatment. 5. GR203040 (0.1 mg kg-1 i.v.) is fully effective against ipecacuanha-induced emesis in the dog. 6. GR203040 is effective against motion- and cisplatin-induced emesis in Suncus murinus. These effects were seen at doses an order of magnitude greater than those shown to be effective against cisplatin in the ferret. 7. In conclusion, GR203040 is a novel anti-Emetic Agent, and the broad spectrum of anti-Emetic activity, together with activity observed in three species, suggests that this compound is worthy of clinical investigation.

C.j. Gardner - One of the best experts on this subject based on the ideXlab platform.

  • gr205171 a novel antagonist with high affinity for the tachykinin nk1 receptor and potent broad spectrum anti Emetic activity
    Regulatory Peptides, 1996
    Co-Authors: C.j. Gardner, D R Armour, D T Beattie, J D Gale, G J Kilpatrick, D J Twissell, A.b. Hawcock, P Ward
    Abstract:

    Abstract It has been demonstrated recently that antagonists of the tachykinin NK1 receptor, specifically CP-99,994 and GR203040, possess anti-Emetic activity in a range of species. To optimise this activity, a series of analogues based around the structure of GR203040 have been synthesised and their affinity at the human tachykinin NK1 receptor determined. In addition, the potency of these analogues to inhibit emesis induced in the ferret by whole-body X-irradiation has been examined. A range of substitutions at the C-1 position of the tetrazole moiety in GR203040 were explored in vitro and in vivo. The trifluoromethyl compound, GR205171, was the most potent antagonist with regard to the ability to inhibit emesis induced by X-irradiation. This compound was demonstrated to have a broad spectrum of anti-Emetic activity, inhibiting emesis in the ferret induced by cisplatin, cyclophosphamide, morphine, ipecacuanha and copper sulphate. Furthermore, emesis was also inhibited in the house-musk shrew, Suncus murinus, when induced by either motion or cisplatin, and in the dog when induced by ipecacuanha. GR205171 has the most potent anti-Emetic activity of any tachykinin NK1 receptor antagonist described to date. The compound is orally active in the ferret and dog, long-lasting, and warrants further investigation as a potential broad-spectrum anti-Emetic Agent.

  • the broad spectrum anti Emetic activity of the novel non peptide tachykinin nk1 receptor antagonist gr203040
    British Journal of Pharmacology, 1995
    Co-Authors: C.j. Gardner, J D Gale, G J Kilpatrick, D J Twissell, C.c. Jordan, Tim J Dale, Chas Bountra, P Ward
    Abstract:

    1. Following our earlier observations that the tachykinin NK1 receptor antagonist CP-99,994 is an effective anti-Emetic in ferrets, we have examined the anti-Emetic effects of a more potent and novel NK1 receptor antagonist, GR203040, against various Emetic stimuli in the ferret, dog and house musk shrew (Suncus murinus). 2. In ferrets, GR203040 (0.1 mg kg-1 s.c. or i.v.) is effective against emesis induced by radiation, cisplatin, cyclophosphamide, copper sulphate, ipecacuanha or morphine. 3. In animals in which emesis had been established with cisplatin, GR203040 (1 mg kg-1 s.c.) was fully effective as an interventional treatment. No further emesis was seen in animals treated with GR203040 whilst saline-treated animals continued to vomit. 4. GR203040 (0.1 mg kg-1 s.c.) retains anti-Emetic efficacy in the ferret, even when given as a 6 h pretreatment, indicating that this compound has a long duration of action. The compound is also effective orally at the same dose, when given as a 90 min pretreatment. 5. GR203040 (0.1 mg kg-1 i.v.) is fully effective against ipecacuanha-induced emesis in the dog. 6. GR203040 is effective against motion- and cisplatin-induced emesis in Suncus murinus. These effects were seen at doses an order of magnitude greater than those shown to be effective against cisplatin in the ferret. 7. In conclusion, GR203040 is a novel anti-Emetic Agent, and the broad spectrum of anti-Emetic activity, together with activity observed in three species, suggests that this compound is worthy of clinical investigation.

Kn Sunil Kumar - One of the best experts on this subject based on the ideXlab platform.

  • A Clinico-analytical Study on Seed of Wrightia antidysenterica Linn. as a Therapeutic Emetic Agent (Vamaka Yoga) in the Management of Psoriasis.
    Pharmacognosy Research, 2016
    Co-Authors: Nirupam Bhattacharyya, Muralidhar P Pujar, Ashutosh Chaturvedi, M Ashvini Kumar, Kn Sunil Kumar
    Abstract:

    Objectives: Wrightia antidysenterica Linn. (WA) is male variety Kutaja stated to be potent therapeutic Emetic Agent in skin disorders. Expulsion of doshas through oral route is termed as Vamana Karma (VK) (therapeutic emesis). However, so far, its utility for Vamana is not explored in detail, therefore there is a need to revalidate the utility of WA for Vamana. Hence, the above study was conducted to ascertain the efficacy as a therapeutic Emetic Agent (vamaka yoga) in the management of psoriasis along with quality control and standardization of this herb. Materials and Methods: The drug was standardized as per analytical procedures in Pharmacopeias. Thirty patients of psoriasis fulfilling inclusion criteria were taken for the study and Vamana with WA was conducted. Criteria were prepared to assess the signs and Symptoms of psoriasis. VK was assessed using the classical Lakshanas (features) such as Anthiki shudhi (Ending symptoms of emesis), Vaigiki shudhi (features of vomiting bouts), Maniki shudhi (Quantitative and qualitative purification), complications. Result: VK with WA showed significant relief in parameters of psoriasis such as scaling, itching, candle grease sign (P < 0.001), and psoriasis area and severity index score (P = 0.001). In VK with WA, mean number of Vegas (vomiting bouts) was 6.91. 66% patients showing quantitative purification between 301 and 600 ml. 73.33% showed all Symptoms of purification. 73.33% patients showed Kaphanta vamana (Moderate expulsion of desire humor). In the level of biopurification, 66.66% patients showed moderated purification. No complication was noted with moderate drug palatability. Conclusion: Pharmacopeial analytical study showed its standardized values for testing the drug used for the study. It is proved as potent therapeutic Emetic Agent with no complication showed its clinical benefits over skin disorder like psoriasis.

  • A Clinico-analytical Study on Seed of Wrightia antidysenterica Linn. as a Therapeutic Emetic Agent (Vamaka Yoga) in the Management of Psoriasis.
    Pharmacognosy research, 2016
    Co-Authors: Nirupam Bhattacharyya, Muralidhar P Pujar, Ashutosh Chaturvedi, M Ashvini Kumar, B A Lohith, Kn Sunil Kumar
    Abstract:

    Wrightia antidysenterica Linn. (WA) is male variety Kutaja stated to be potent therapeutic Emetic Agent in skin disorders. Expulsion of doshas through oral route is termed as Vamana Karma (VK) (therapeutic emesis). However, so far, its utility for Vamana is not explored in detail, therefore there is a need to revalidate the utility of WA for Vamana. Hence, the above study was conducted to ascertain the efficacy as a therapeutic Emetic Agent (vamaka yoga) in the management of psoriasis along with quality control and standardization of this herb. The drug was standardized as per analytical procedures in Pharmacopeias. Thirty patients of psoriasis fulfilling inclusion criteria were taken for the study and Vamana with WA was conducted. Criteria were prepared to assess the signs and Symptoms of psoriasis. VK was assessed using the classical Lakshanas (features) such as Anthiki shudhi (Ending symptoms of emesis), Vaigiki shudhi (features of vomiting bouts), Maniki shudhi (Quantitative and qualitative purification), complications. VK with WA showed significant relief in parameters of psoriasis such as scaling, itching, candle grease sign (P < 0.001), and psoriasis area and severity index score (P = 0.001). In VK with WA, mean number of Vegas (vomiting bouts) was 6.91. 66% patients showing quantitative purification between 301 and 600 ml. 73.33% showed all Symptoms of purification. 73.33% patients showed Kaphanta vamana (Moderate expulsion of desire humor). In the level of biopurification, 66.66% patients showed moderated purification. No complication was noted with moderate drug palatability. Pharmacopeial analytical study showed its standardized values for testing the drug used for the study. It is proved as potent therapeutic Emetic Agent with no complication showed its clinical benefits over skin disorder like psoriasis. Seeds of Wrightia antidysenterica (WA) Linn. free from any foreign matter were selected for the study. Loss on drying revealed 6.535% moisture content; total ash indicating of total inorganic content was found to be 5.12%; acid insoluble ash is the acid insoluble part of total ash, mainly silica, WA showed 0.393% acid insoluble ash; ethanol and water soluble extractive is indicative of percentage active constituents were found to be 25.66 and 20.854%, respectively. High-performance thin layer chromatography fingerprinting profiles of WA under 254 nm showed the presence of 7 spots (all in green) at Rf values ranging from 0.21 to 0.88. Under 366 nm there were 4 prominent spots (all in fluorescent) at Rf 0.49 to 0.82 and, when scanned under white light 620 nm following derivatization with vanillin sulfuric acid 6 spots (in different colors) were evident at Rf 0.28 to 0.58. Among these spot with Rf of 0.58 was common when visualized under all the three methods. Rf values by densitometric scan of WA showed 12 peaks at 254 nm and 5 peaks at 366 nm. However, in clinical trial, it was found to be a potent Emetic Agent without any complication. Abbreviations Used: WA: Wrightia antidysenterica; Linn.; VK: Vamana karma; BT: Before treatment; FP: Freidman's P value; CHS: Chi-square value; NR: Negative ranks; PR: Positive ranks; N: Sample number, AS: Austipz sign; CG: Candle grease test; SSL: Samyak Snigdha Lakshana.

J D Gale - One of the best experts on this subject based on the ideXlab platform.

  • gr205171 a novel antagonist with high affinity for the tachykinin nk1 receptor and potent broad spectrum anti Emetic activity
    Regulatory Peptides, 1996
    Co-Authors: C.j. Gardner, D R Armour, D T Beattie, J D Gale, G J Kilpatrick, D J Twissell, A.b. Hawcock, P Ward
    Abstract:

    Abstract It has been demonstrated recently that antagonists of the tachykinin NK1 receptor, specifically CP-99,994 and GR203040, possess anti-Emetic activity in a range of species. To optimise this activity, a series of analogues based around the structure of GR203040 have been synthesised and their affinity at the human tachykinin NK1 receptor determined. In addition, the potency of these analogues to inhibit emesis induced in the ferret by whole-body X-irradiation has been examined. A range of substitutions at the C-1 position of the tetrazole moiety in GR203040 were explored in vitro and in vivo. The trifluoromethyl compound, GR205171, was the most potent antagonist with regard to the ability to inhibit emesis induced by X-irradiation. This compound was demonstrated to have a broad spectrum of anti-Emetic activity, inhibiting emesis in the ferret induced by cisplatin, cyclophosphamide, morphine, ipecacuanha and copper sulphate. Furthermore, emesis was also inhibited in the house-musk shrew, Suncus murinus, when induced by either motion or cisplatin, and in the dog when induced by ipecacuanha. GR205171 has the most potent anti-Emetic activity of any tachykinin NK1 receptor antagonist described to date. The compound is orally active in the ferret and dog, long-lasting, and warrants further investigation as a potential broad-spectrum anti-Emetic Agent.

  • the broad spectrum anti Emetic activity of the novel non peptide tachykinin nk1 receptor antagonist gr203040
    British Journal of Pharmacology, 1995
    Co-Authors: C.j. Gardner, J D Gale, G J Kilpatrick, D J Twissell, C.c. Jordan, Tim J Dale, Chas Bountra, P Ward
    Abstract:

    1. Following our earlier observations that the tachykinin NK1 receptor antagonist CP-99,994 is an effective anti-Emetic in ferrets, we have examined the anti-Emetic effects of a more potent and novel NK1 receptor antagonist, GR203040, against various Emetic stimuli in the ferret, dog and house musk shrew (Suncus murinus). 2. In ferrets, GR203040 (0.1 mg kg-1 s.c. or i.v.) is effective against emesis induced by radiation, cisplatin, cyclophosphamide, copper sulphate, ipecacuanha or morphine. 3. In animals in which emesis had been established with cisplatin, GR203040 (1 mg kg-1 s.c.) was fully effective as an interventional treatment. No further emesis was seen in animals treated with GR203040 whilst saline-treated animals continued to vomit. 4. GR203040 (0.1 mg kg-1 s.c.) retains anti-Emetic efficacy in the ferret, even when given as a 6 h pretreatment, indicating that this compound has a long duration of action. The compound is also effective orally at the same dose, when given as a 90 min pretreatment. 5. GR203040 (0.1 mg kg-1 i.v.) is fully effective against ipecacuanha-induced emesis in the dog. 6. GR203040 is effective against motion- and cisplatin-induced emesis in Suncus murinus. These effects were seen at doses an order of magnitude greater than those shown to be effective against cisplatin in the ferret. 7. In conclusion, GR203040 is a novel anti-Emetic Agent, and the broad spectrum of anti-Emetic activity, together with activity observed in three species, suggests that this compound is worthy of clinical investigation.

D J Twissell - One of the best experts on this subject based on the ideXlab platform.

  • gr205171 a novel antagonist with high affinity for the tachykinin nk1 receptor and potent broad spectrum anti Emetic activity
    Regulatory Peptides, 1996
    Co-Authors: C.j. Gardner, D R Armour, D T Beattie, J D Gale, G J Kilpatrick, D J Twissell, A.b. Hawcock, P Ward
    Abstract:

    Abstract It has been demonstrated recently that antagonists of the tachykinin NK1 receptor, specifically CP-99,994 and GR203040, possess anti-Emetic activity in a range of species. To optimise this activity, a series of analogues based around the structure of GR203040 have been synthesised and their affinity at the human tachykinin NK1 receptor determined. In addition, the potency of these analogues to inhibit emesis induced in the ferret by whole-body X-irradiation has been examined. A range of substitutions at the C-1 position of the tetrazole moiety in GR203040 were explored in vitro and in vivo. The trifluoromethyl compound, GR205171, was the most potent antagonist with regard to the ability to inhibit emesis induced by X-irradiation. This compound was demonstrated to have a broad spectrum of anti-Emetic activity, inhibiting emesis in the ferret induced by cisplatin, cyclophosphamide, morphine, ipecacuanha and copper sulphate. Furthermore, emesis was also inhibited in the house-musk shrew, Suncus murinus, when induced by either motion or cisplatin, and in the dog when induced by ipecacuanha. GR205171 has the most potent anti-Emetic activity of any tachykinin NK1 receptor antagonist described to date. The compound is orally active in the ferret and dog, long-lasting, and warrants further investigation as a potential broad-spectrum anti-Emetic Agent.

  • the broad spectrum anti Emetic activity of the novel non peptide tachykinin nk1 receptor antagonist gr203040
    British Journal of Pharmacology, 1995
    Co-Authors: C.j. Gardner, J D Gale, G J Kilpatrick, D J Twissell, C.c. Jordan, Tim J Dale, Chas Bountra, P Ward
    Abstract:

    1. Following our earlier observations that the tachykinin NK1 receptor antagonist CP-99,994 is an effective anti-Emetic in ferrets, we have examined the anti-Emetic effects of a more potent and novel NK1 receptor antagonist, GR203040, against various Emetic stimuli in the ferret, dog and house musk shrew (Suncus murinus). 2. In ferrets, GR203040 (0.1 mg kg-1 s.c. or i.v.) is effective against emesis induced by radiation, cisplatin, cyclophosphamide, copper sulphate, ipecacuanha or morphine. 3. In animals in which emesis had been established with cisplatin, GR203040 (1 mg kg-1 s.c.) was fully effective as an interventional treatment. No further emesis was seen in animals treated with GR203040 whilst saline-treated animals continued to vomit. 4. GR203040 (0.1 mg kg-1 s.c.) retains anti-Emetic efficacy in the ferret, even when given as a 6 h pretreatment, indicating that this compound has a long duration of action. The compound is also effective orally at the same dose, when given as a 90 min pretreatment. 5. GR203040 (0.1 mg kg-1 i.v.) is fully effective against ipecacuanha-induced emesis in the dog. 6. GR203040 is effective against motion- and cisplatin-induced emesis in Suncus murinus. These effects were seen at doses an order of magnitude greater than those shown to be effective against cisplatin in the ferret. 7. In conclusion, GR203040 is a novel anti-Emetic Agent, and the broad spectrum of anti-Emetic activity, together with activity observed in three species, suggests that this compound is worthy of clinical investigation.