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applications of these drugs are contraindicated from the points of gastroenterologist. 4. We earlier proved clearly that the small doses of capsaicin (given orally in doses of nanogram to microgram / kg in animal experiments and 200 to 800 µg in human observations) prevents the aspirin, indomethacin (a mixed COX-1 and COX-2 inhibitor)-induced gastrointestinal mucosal damage. Aims: 1. The development and pharmaceutically production of the planned production of new gastrointestinal mucosal protective drug (capsaicin alone and/or capsaicin in combination with different nonsteroidal anti-inflammatory drugs) for the use in human healthy beings and in patients. 2. For the development and production of a new drug, we had to respect the following aspects: a. the knowledge of the chemical composition of natural origin capsaicin(oids); b. problems of the analytical measurements of capsaicin(oids) in the biological samples (in animals and humans); c. correct and complete preclinical dossier; d. correct dossier of acute and chronic toxicological studies with capsaicin (including the different tests) in two speciments of animal experiments; e. existence of a complete drug master file (DMF); f. the exclusion of pesticides, fusariums, aflatoxin and other toxicological agents (which are used during the plant cultivation in the different countries) from the capsaicin(oids) preparations used for drug production; g. to collect the necessary permissions from the different international and national authrorities before starting of pharmaceutical production of drug alone or in combinations; h. different pharmaceutical controlling measurements and other pharmaceutical aspects of planned drug or drug combinations (such as stability, drug preparation, different pharmaceutical technologies, etc.); i. preparation of different protocols for human human phase examinations (especially for human phase I.); j. to receive the permissions from the the different national authorities to carried out the prepared protocols before starting of the classical pharmacological studies; k. to gather the necessary numbers of experts from the very different scientific fields, who are able to solve all of above mentioned scientific, pharmaceutical, research problems (in animal experiments and in human observations); l. to find accredited institutes to perform human clinical pharmacological (phase) examinations. 2. When we solved all of above scientific problems, the human phase I. examinations with capsaicin alone and with combination+aspirin and capsaicin+diclofenac, the human phase I. examinations were in the

Our results show that carvedilol can modulate the reactive-oxygen-species-induced signaling through poly- and mono(ADP-ribosyl)ation reactions, the NAD(+) catabolism in postischemic perfused hearts and has a marked scavenger effect on free radical generator-induced red blood cell membrane damage. All these findings may play an important role in the beneficial effects of carvedilol treatment in different cardiovascular diseases.

(1) The capsaicin used in the physiological and pharmacological observations (in animals and human beings) chemically represents different chemical compounds, which can be obtained from the plants (paprika, chilli, etc.), (2) capsaicinoids are able to modify the capsaicin-sensitive afferent nerves, which have principle roles in the defence of different organs (including the gastrointestinal tract [against the different chemicals, heat, strech, chemical millieu-induced damage], (3) the application of capsaicin (capsaicinoids) can be repeated for the beneficial effects on the gastrointestinal tract as those in animal experiments. After this interdisciplinary and critical review, this paper demonstrates the well-planned research pathways of the discoveries of capsaicinoids from plant chemistry, via physiology, pharmacology and toxicology in animal experiments and human observations.