Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1994-10-13
1998-02-03
Killos, Paul J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
A61K 31535
Patent
active
057144834
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to an antitussive.
BACKGROUND ART
Conventional antitussives are provided by mixing drugs which variously affect central nervous system, such as codeine and dextromethorphan. However, these drugs have serious side effects such as drug dependence and psychotomimetic, so that close attention should be paid when using these antitussives.
In recent years, antitissive effect of .mu. and .kappa. agonists of opioid is drawing attention. However, conventional agonists such as morphine and codeine have problems that they cause drug dependence and conventional .kappa.-agonists have problems that they cause aversion and psychotomimetic. Under these circumstances, an excellent antitussive free from psychotomimetic, drug dependence and aversion is demanded.
DISCLOSURE OF THE INVENTION
An object of the present invention is to provide a novel antitussive having high activity, of which action mechanism is different from that of the above-mentioned conventional antitussives having serious side effects such as drug dependence, psychotomimetic and aversion, which is free from the side effects that the conventional antitussives have, and which may also be used as an oral drug.
The present inventors intensively studied to develop the above-mentioned ideal antitussive to discover that antagonists of .delta. opioid receptor have strong antitussive effect, which have an action mechanism totally different from that of the conventional morphine, codeine and dextromethorphan, thereby completing the present invention. Unlike the agonists of opioid, the .delta.-antagonists do not cause drug dependence, psychotomimetic and aversion, so that selective antitussive effect can be expected.
That is, the present invention provides an antitussive comprising as an effective ingredient a .delta.-opioid antagonist or a pharmaceutically acceptable salt thereof.
By the present invention, an antitussive of which action mechanism is totally different from that of the conventional antitussives having serious side effects such as drug dependence, psychotomimetic and aversion, which has a high activity and which may also be orally administered was provided.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 shows the influence by Compound 1 (naltrindole: NTI) on capsaicin-induced cough.
FIG. 2 shows the suppression rate of number of cough after 15 minutes from the administration of Compound 1.
FIG. 3 shows the influence by Compound 3 (BNTX) on capsaicin-induced cough.
BEST MODE FOR CARRYING OUT THE INVENTION
As mentioned above, the antitussive according to the present invention comprises as an effective ingredient a .delta.-antagonist or a pharmaceutically acceptable salt thereof.
Examples of the .delta.-antagonists include those represented by the following formula (I): ##STR1## {wherein R.sup.1 represents C.sub.1 -C.sub.5 alkyl, C.sub.4 -C.sub.7 cycloalkylalkyl, C.sub.5 -C.sub.7 cycloalkenylalkyl, C.sub.6 -C.sub.12 aryl, C.sub.7 -C.sub.13 aralkyl, C.sub.4 -C.sub.7 alkenyl, allyl, C.sub.1 -C.sub.5 furan-2-ylalkyl or C.sub.1 -C.sub.5 thiophene-2-ylalkyl; R.sup.2 represents hydrogen, hydroxy, C.sub.1 -C.sub.5 alkanoyloxy, C.sub.1 -C.sub.5 alkoxy, C.sub.7 -C.sub.13 arylcarbonyloxy or C.sub.7 -C.sub.13 aralkyloxy; R.sup.3 represents hydrogen, hydroxy, C.sub.1 -C.sub.5 alkanoyloxy, C.sub.1 -C.sub.5 alkoxy, C.sub.7 -C.sub.13 arylcarbonyloxy or C.sub.7 -C.sub.13 aralkyloxy; X represents ##STR2## (wherein R.sup.4 represents hydrogen, C.sub.1 -C.sub.5 alkyl or C.sub.7 -C.sub.13 aralkyl; R.sup.5, R.sup.6 and R.sup.7 independently represent hydrogen, fluorine, chlorine, bromine, nitro, C.sub.1 -C.sub.5 alkyl, C.sub.1 -C.sub.5 alkoxy, isothiocyanato, iodine, trifluoromethyl, trifluoromethoxy, cyano, phenyl, C.sub.1 -C.sub.3 hydroxyalkyl, SR.sup.8, SOR.sup.8, SO.sub.2 R.sup.8, (CH.sub.2).sub.m CO.sub.2 R.sup.8 (wherein m represents an integer of 0-3, R.sup.8 represents C.sub.1 -C.sub.5 alkyl), SO.sub.2 NR.sup.9 R.sup.10, CONR.sup.9 R.sup.10, (CH.sub.2).sub.n NR.sup.9 R.sup.10 (wherein n represents an integer of 0-3,
REFERENCES:
patent: 4816586 (1989-03-01), Portoghese
patent: 5332818 (1994-07-01), Nagase et al.
Eur. J. Pharmacol., vol. 249, No. 2, J. Kamei et al., "Antitussive effects of naltrindole, . . . "; 1993: 161-165.
Eur. J. Pharmacol., vol. 218, No. 1, P. Portoghese et al., "A highly selective .delta..sub.1 -opioid receptor antagonist: . . . "; 1992: 195-196.
J. Med. Chem., vol. 34, No. 5, P. Portoghese et al., "Role of Spacer . . . " 1991: 1715-1720.
J. Med. Chem., vol. 33, No. 6, P. Portoghese et al., "Design of Peptidomimetic . . . " 1990: 1714-1720.
CA 117:83213 1992.
Endo Takashi
Kamei Junzo
Kawai Koji
Nagase Hiroshi
Killos Paul J.
Toray Industries Inc.
LandOfFree
Antitussive does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Antitussive, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Antitussive will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-662512