Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1997-12-18
2000-10-31
Raymond, Richard L.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
5142358, 5142362, 51425504, 514264, 514305, 514314, 514329, 514357, 514414, 514416, 514648, 514 79, A61K 315377, A61K 3166, A61K 3114
Patent
active
061403245
DESCRIPTION:
BRIEF SUMMARY
This invention relates to the treatment or prevention of motion sickness by the administration of a combination of a tachykinin antagonist, in particular an NK-1 receptor antagonist, and a muscarinic antagonist and/or a histamine antagonist.
Motion sickness can be produced in a number of situations which are reflected in the variety of names given to this condition, including: sea sickness, car sickness, air sickness, swing sickness and space sickness. It will be appreciated however that a subject may develop symptoms of motion sickness without being in motion. For instance, members of an audience watching a cinema film taken from a moving vehicle, such as a fairground ride, may experience symptoms of motion sickness while they themselves remain stationary.
One widely discussed explanation of the cause of motion sickness is the sensory conflict theory. The body perceives its orientation in space and changes thereof through visual input and the vestibular system located in the inner ear: angular acceleration being detected through the semi-circular canals and linear acceleration through otoliths. Other parts of the body may also add confirmatory evidence of motion, for example, cutaneous sensors, muscle spindles and tendon organs. The body will in general assume that the external visual scene as a whole remains stable in space and that gravity does not change in intensity or direction. The sensory conflict theory proposes that motion sickness occurs where infomation about motion obtained through one sensory modality is unsupported, or even contradicted, by the motion information obtained through another (for review, see C. M. Oman, Can. J. Piysiol. Pharmacol., (1990) 68, 294-303).
In a development of this theory, Treisman has proposed an explanation as to why nausea and vomiting should occur in response to sensory conflict (Science, (1977)197, 493-495). It is suggested that conflicting sensory inputs are interpretated centrally as neurophysiological dysfunction caused by poisoning, this being supported by the observation that the brain stem mechanism of orientation and motion also function to detect and respond to certain poisons (for review see K. E. Money, Mechanisms and Control of Emesis, A. L. Bianchi et al (Eds.) Colloques INSERM, John Libbey Eurotext, (1992) 223, 177-184).
Certain drugs have been used both in the prophylaxis and in the treatment of motion-induced emesis, though side-effects may limit their usefulness (see J. R. Rollin Stott, Mechanisms and Control of Emesis, A. L. Bianchi et al (Eds.) Colloques INSERM, John Libbey Eurotext, (1992) 223, 203-212). It has been shown, however, that many drugs which are used to treat nausea and vomiting from other causes (for example, chemotherapy-induced emesis) are ineffective in motion sickness. For instance, the 5-HT.sub.3 antagonist ondansetron (GR 38032F) which possesses potent antiemetic properties in vomiting induced by cancer chemotherapeutic drugs has been shown to have no effect in man on motion sickness induced by cross-coupled stimulation (J. R. R. Stott et al., Br. J. Clin. Pharmac., (1989) 27, 147-157).
The most widely used agents use in the management of motion sickness are muscarinic antagonists and antihistamines (histamine H.sub.1 -receptor antagonists). In general, it is preferable to administer these drugs prophylactically since they are much less effective once severe nausea and vomiting has developed.
The most commonly used muscarinic antagonists include scopolomine (l-hyoscine) and related belladona alkaloids. Antihistamines which have been shown to be effective in the prevention of motion sickness include promethazine, cinnarizine, dimenhydrinate, cyclizine and meclizine.
Scopolamine has proved to be one of the most effective drugs for short duration exposures to provocative motion, however, doses in excess of 0.6 mg are very liable to lead to side-effects, typically light headedness, drowsiness and dry mouth. Furthermore, scopolamine is not recommended for children in whom the therapeutic margin is probably narrower and who are th
REFERENCES:
patent: 5457107 (1995-10-01), Kaufman
patent: 5641777 (1997-06-01), Edmonds-Alt et al.
patent: 5719147 (1998-02-01), Dorn et al.
patent: 5719149 (1998-02-01), Finke et al.
patent: 5747491 (1998-05-01), Haworth et al.
Drug Facts and Comparisons, 1995 Edition, Facts and Comparisons, St. Louis, MO, p. 1324.
C. Bountra, et al., Oncology, vol. 53, No. spl. 1, 1996, pp. 102-109.
Merck Sharp & Dohme Ltd.
Raymond Richard L.
Rose David L.
Thies J. Eric
LandOfFree
Use of a tachykinin antagonist and a muscarinic antagonist and/o does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Use of a tachykinin antagonist and a muscarinic antagonist and/o, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Use of a tachykinin antagonist and a muscarinic antagonist and/o will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2052005