Methods for treatment of drug-induced peripheral neuropathy

Details Methods for treatment of drug-induced peripheral neuropathy Methods for treatment of drug-induced peripheral neuropathy

2001-07-06

2003-10-07

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

06630478

ABSTRACT:

BACKGROUND OF THE INVENTION
This invention is directed to methods for treatment of drug-induced peripheral neuropathy and related conditions, particularly drug-induced peripheral neuropathy associated with the administration of oncolytic drugs.
Many oncolytic or antineoplastic drugs have been developed in recent years. Although such drugs have proven effective in many cases in the treatment of malignancies, they can have severe side effects. One of the most serious and clinically significant side effect is peripheral neuropathy. Many antineoplastic drugs can cause peripheral neuropathy. For some of the most effective drugs, neurotoxicity is dose-limiting. It can force the termination of otherwise successful therapy, or can preclude the repetition of successful therapy. Sensory abnormalities produced by the administration of antineoplastic drugs can range from mild paresthesiae or dysesthesiae to severe neuropathic pain. In some cases, sensory and motor symptoms resolve within days or weeks after the agents are discontinued. However, peripheral neuropathy can be a chronic painful and disabling condition. The mechanisms that produce peripheral neuropathy as a consequence of the administration of oncolytic drugs are largely unknown (R. C. Polomano & G. J. Bennett, “Chemotherapy-evoked Painful Peripheral Neuropathy,”
Pain Med.
2: 8-14 (2001); S. De Santis et al., “Patients Treated with Antitumor Drugs Displaying Neurological Deficits Are Characterized by a Low Circulating Level of Nerve Growth Factor,”
Clin. Cancer Res.
6: 90-95 (2000); K. Hayakawa et al., “NGF Prevention of Neurotoxicity Induced by Cisplatin, Vincristine and Taxol Depends on Toxicity of Each Drug and NGF Treatment Schedule: In Vitro Study of Adult Rat Sympathetic Ganglion Explants,”
Brain Res.
794: 313-319 (1998)).
Accordingly, there is a need for more efficient methods of combating drug-induced peripheral neuropathy, particularly peripheral neuropathy induced by the administration of oncolytic drugs. Preferably, such methods should not interfere with cancer treatment or block the activity of the oncolytic drugs. Such methods should also not induce other side effects and should be well tolerated by cancer patients. Preferably, such methods should also combat peripheral neuropathy for all oncolytic drugs and should not depend on specific interactions with each individual oncolytic drug. There is a particular need for methods that can stimulate nerve growth or regeneration, particularly without inducing hyperalgesia.
SUMMARY
One embodiment of the present invention is a method of treating drug-induced peripheral neuropathy comprising administering to a patient with drug-induced peripheral neuropathy an effective quantity of an effective quantity of a compound comprising: (1) a moiety A selected from the group consisting of a purine moiety, a purine analogue, a tetrahydroindolone moiety, a tetrahydroindolone analogue, a pyrimidine moiety, a pyrimidine analogue and aminocarboxaminoimidazoles; (2) a hydrocarbyl moiety L of 1 to 6 carbon atoms that is linked to the moiety A and that can be cyclic, with the hydrocarbyl moiety being optionally substituted with one or more substituents selected from the group consisting of lower alkyl, amino, hydroxy, lower alkoxy, lower alkylamino, lower alkylthio, and oxo; and (3) a moiety B that is linked to the moiety L though a carbonyl group wherein B is —OZ or N(Y
1
)—D, where Z is hydrogen, alkyl, aryl, heteroaryl, cycloalkyl, aralkyl, or heteroaralkyl; D is a moiety that promotes absorption of the compound; and Y
1
is hydrogen, alkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, alkanoyl, aroyl, heteroaroyl, aralkanoyl, heteroaralkanoyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, aralkylsulfonyl, heteroaralkylsulfonyl, alkoxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, aralkoxycarbonyl, heteroaralkoxycarbonyl, alkylaminocarbonyl, arylaminocarbonyl, heteroarylaminocarbonyl, aralkylaminocarbonyl, or heteroaralkylaminocarbonyl, in which the alkyl portions can be cyclic and can contain from 1 to 3 heteroatoms, which can be N, O, or S.
The purine moiety can be selected from the group consisting of hypoxanthine and guanine, as well as other purine moieties. A number of purine derivatives suitable for use in methods according to the present invention are disclosed. In addition to these purines, analogues of naturally occuring purines defined above, tetrahydroindolones, tetrahydroindolone analogues, pyrimidines, pyrimidine analogues and aminocarboxaminoimidazoles, which maintain the proposed pharmacophore between the 6, 5, 4, and 9 positions on the purine molecule, may be used as alternatives to purines.
Preferably, the compound is capable of passing through the blood-brain barrier.
Typically, the administration of the compound induces peripheral nerve sprouting in the skin of the patient to whom the purine derivative is administered. The peripheral nerve sprouting can be nociceptive nerve sprouting. Typically, the nociceptive nerve sprouting is induced without the occurrence of hyperalgesia.
The drug-induced peripheral neuropathy can be induced by the administration of an oncolytic drug such as a vinca alkaloid, cisplatin, paclitaxel, suramin, altretamine, carboplatin, chlorambucil, cytarabine, dacarbazine, docetaxel, etoposide, fludarabine, ifosfamide with mesna, tamoxifen, teniposide, or thioguanine. Methods according to the present invention are particularly significant in treating drug-induced peripheral neuropathy arising from the administration of vincristine, paclitaxel, or cisplatin.


REFERENCES:
patent: 3300380 (1967-01-01), Gray et al.
patent: 3321369 (1967-05-01), Glasky et al.
patent: 3438968 (1969-04-01), Glasky et al.
patent: 3666856 (1972-05-01), Elion et al.
patent: 4035486 (1977-07-01), Laborit
patent: 4138562 (1979-02-01), Vince
patent: 4221794 (1980-09-01), Simon et al.
patent: 4221909 (1980-09-01), Simon et al.
patent: 4221910 (1980-09-01), Giner-Sorolla
patent: 4315920 (1982-02-01), Schaeffer et al.
patent: 4340726 (1982-07-01), Simon et al.
patent: 4347360 (1982-08-01), Ogilvie
patent: 4451478 (1984-05-01), Simon et al.
patent: 4643992 (1987-02-01), Goodman et al.
patent: 4952693 (1990-08-01), Sircar et al.
patent: 5023244 (1991-06-01), Goto et al.
patent: 5091432 (1992-02-01), Glasky
patent: 5093318 (1992-03-01), Goodman et al.
patent: 5187162 (1993-02-01), Marangos et al.
patent: 5237051 (1993-08-01), Garbers et al.
patent: 5256677 (1993-10-01), Sham et al.
patent: 5376642 (1994-12-01), Yarchoan et al.
patent: 5447939 (1995-09-01), Glasky et al.
patent: 5565437 (1996-10-01), Marquez et al.
patent: 5595901 (1997-01-01), Rocancourt et al.
patent: 5795756 (1998-08-01), Johnson et al.
patent: 5801159 (1998-09-01), Miller et al.
patent: 5801184 (1998-09-01), Glasky et al.
patent: 5948771 (1999-09-01), Danziger
patent: 6027936 (2000-02-01), Glasky
patent: WO 99/56550 (1999-11-01), None
patent: WO 99/57119 (1999-11-01), None
patent: WO 99/57120 (1999-11-01), None
Stedman's Medical Dictionary, pp. 243-244 (1995).*
N.W. Tietz, ed., “Textbook of Clinical Chemistry” (W.B. Saunders Co., Philadelphia, 1986), pp. 882-886.
G.A. Lyles & B. A. Callingham, “The Effects of Thyroid Hormones on Monoamine Oxidase in the Rat Heart,”J. Pharm. Pharmacol.26:921-930 (1974).
S.K. Gupta & R.K. Mishra, “Desensitization of D1Dopamine Receptors Down-Regulates the Gs&agr; Subunit of G Protein in SK-N-MC Neuroblastoma Cells,”J. Mol. Neurosci.4: 117-123 (1993).
S.K. Gupta & R.K. Mishra, “Up-Regulation of D1Dopamine Receptors in SK-N-MC Cells After Chronic Treatment with SCH 23390,”Neurosci. Res. Commun.15: 157-166 (1994).
P.W. Baures et al., “Design, Synthesis, X-Ray Analysis, and Dopamine Receptor-Modulating Activity of Mimics of the C5' Hydrogen-Bonded Conformation in the Peptidomimetic 2-Oxo-3-(R)-[(2(S)-Pyrrolidinylcarbonyl)amino]-1-Pyrrolidineacetamide,”J. Med. Chem.37: 3677-3683 (1994).
J.E. Savelli et al., “Modulation of N-Methyl-D-Aspartate (NMDA) Antagonist-Induced Darting Behaviour by the Peptidomimetic PAMTA,”,Brain Res.682: 41-49 (1995).
K.A. Jacobso

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