Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
1999-07-12
2003-06-24
Spivack, Phyllis G. (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
Reexamination Certificate
active
06583151
ABSTRACT:
TECHNICAL FIELD
The present invention relates to a remedy for drug dependence. In addition, the present invention relates to a dopamine-release inhibitor, in which dopamine is heavily associated with drug dependence.
BACKGROUND ART
When a person repeatedly take a natural substance such as opium, cocaine, or marijuana, or takes a specific drug such as heroin, barbiturates, or stimulants, it is impossible to suddenly withhold the drug. Then, their major goal in life tends to focus on obtaining these substances and drugs. In addition, brutal crimes may be provoked. Moreover, serious incidents, which affect the state of the nation, may also be provoked. There is substantially the same underlying cause in these problems of drug abuse as in habituation to consuming common substances, for example, alcohol or tobacco.
World Health Organization (WHO) defines both drug dependence and drug abuse. That is, drug dependence is defined as follows: “A state, psychic and sometimes also physical, resulting from the interaction between a living organism and a drug, characterized by behavioural and other responses that always include a compulsion to take the drug on a continuous or periodic basis in order to experience its psychic effects, and sometimes to avoid the discomfort of its absence.” Drug dependence is further classified as a state of psychic dependence on a drug, that is, psychic dependence, or a state in which a body is adapted to existing the drug, that is, physical dependence.
The WHO classifies drugs which become addictive into nine groups, that is, 1. alcohol, 2. amphetamines, 3. barbiturates, 4. marijuana, 5. cocaine, 6. hallucinogens, 7. khat, 8. opiates, and 9. organic solvents. All the drugs classified into the nine groups, to which dependence may be developed, also show psychic dependence. In addition, three groups, that is, opiates, barbiturates, and alcohol, may be accompanied by physical dependence. At present, among these drugs which develop dependence, opiates, barbiturates, cocaine, and amphetamines are available for clinical use.
With respect to international laws relevant to dependence-producing drugs, there are the “Single Convention Treaty on Narcotic Drugs” (1961) and the “The Convention on Psychotropic Substances” (1971). Under the above-mentioned two treaties, all countries are to make a concerted effort to conduct strict inspections of international distribution of narcotics and prevent narcotics from being illicitly distributed. As drug abuse expands throughout the world, international regulation becomes stricter. Recently, drugs capable of being abused have increased both in kind and in variety. On the other hand, since exchange of goods and travel have been internationally increased and an information network has been developed, cases of psychotropic drug abuse have increased in addition to cases of narcotics, marijuana, and stimulant abuse. In addition, the drug abuse epidemic area is also spreading throughout the world. For example, recently, narcotics abuse has significantly increased in countries in North America, Central and South America, Southeast Asia, Middle East, and Europe. In particular, the cocaine abuse problem has become a deep social ill in South America, North America, Europe and the like. On the other hand, the stimulants abuse problem has also spread in Japan, North America, and Europe. Furthermore, at present, other psychotropic drug abuses have also increased in these countries.
With respect to a remedy for drug dependence, particular drugs are not usually applied other than drugs used for symptomatic treatment. The main treatment is psychotherapy which is aimed at self-awareness, replacing a dependence-producing drug with a drug which is less dependent, or gradually-decreasing drug treatment. With respect to symptomatic treatment, antianxiety drugs such as diazepam and flunitrazepam, and short-acting barbiturates have been initially used for treatment for acute toxipathy. An antipsychotic agent such as haloperidol or phenotiazines has been used for treatment of acute psychoses. However, the items of concern involve adverse effect such as psychogenesis peculiar to central nervous system sedatives in treatments using drugs such as diazepam, flunitrazepam, or barbiturates. The items of concern involve adverse effects such as psychogenesis peculiar to psychotropic drugs in treatment using drugs such as haloperidol or phenotiazines, so that there is the possibility that drug dependence is replaced by psychotropic drug dependence. (Alcohol and Drug Dependence, Basic Research and Clinical Research, Kenshirou Oohara, Sakutarou Tadokoro (Kaneharasyuppan); Drug Dependence, Mitsumoto Satou, Susumu Fukui (Sekaihokentuusinsya)).
A drug reaction in which after the drug is given to a living organism, drug-seeking behavior or drug-taking behavior are more frequently induced, is defined as a reinforcing effect or a reward effect. These effects caused by the dependence-producing drugs are closely related to an intracerebral dopamine nervous system. The intracerebral dopamine nervous system is roughly classified into two systems, that is, a nigrostriatal system and a mesolimbic system which projects from an ventral tagmental area to a nucleus accumbens. There have been many reports which indicate the reinforcing effect or the reward effect is related to the mesolimbic system.
For example, cocaine, that is a central nervous system stimulant, affects neurosynapses in the nucleus accumbens so as to accelerate dopamine release from dopamine neuroterminals and to inhibit the uptake thereof, so that an amount of dopamine which binds to dopamine receptors increases and nerve activities are facilitated. Therefore, onset of psychic dependence seems to be triggered. On the other hand, since opioid &kgr; receptor agonists inhibit dopamine release in the nucleus accumbens (Japanese Journal of Pharmacology. 109: 165-173, 1997), the opioid &kgr; receptor agonists may suppress the reward effect of cocaine and hold promise as a remedy for psychic cocaine dependence. At present, opioid &kgr; receptor agonists, however, have not been applied in practical use for a remedy for cocaine dependence.
In addition, with respect to the relationship between opiates and their reward effect in drug dependence, it is known that opiates not only have analgesic activity but also function as a chemical mediator for the reward effect. The opioid receptors are classified into &mgr;, &dgr;, and &kgr; receptors. Among them, it was initially reported that &mgr; receptor agonists such as morphine showed the reward effect (T. Suzuki et al., Eur. J. Pharmacol. 205, 85, 1991). It has been reported that &mgr; or &dgr; receptor agonistic endogenous opioid peptides such as &bgr;-endorphins and enkephalins also show the reward effect (T. Suzuki et al., Jpn. J. Pharmacol. 66, 131, 1994).
Furthermore, opioid receptors are known to relate to a dopamine nervous system. The opioid &mgr; receptors are distributed in high density in a ventral tegmental area in which cell sonata of the mesolimbic system exist, so that they inhibit an inhibitory &ggr;-aminobutyric acid (GABA) nervous system, that is, interneurons, and stimulate the mesolimbic system. As a result, it is suggested that when a &mgr; receptor agonist is systemically administered or microinjected into the ventral tegmental area, dopamine release in the projected nucleus accumbens seems to be significantly increased. On the other hand, &dgr;, and &kgr; opioid receptors are known to be distributed in high density in the projected area, that is, nucleus accumbens in the mesolimbic system. When &dgr; opioid receptors are activated, similarly to &mgr; opioid receptors, they seem to inhibit the inhibitory GABA nervous system, that is, interneurons, and to facilitate dopamine release in the nucleus accumbens. In contrast, &kgr; receptor agonists do not show the reward effect in a drug self-administration (T. Suzuki et al., Brain Res. 602, 45, 1993). As described above, it is reported that when a &kgr; receptor agonist such as U-50488H which activates &kgr
Endoh Takashi
Inada Hideaki
Kawamura Kuniaki
Nagase Hiroshi
Oshima Koji
Birch & Stewart Kolasch & Birch, LLP
Spivack Phyllis G.
Toray Industries Inc.
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