Methods, compositions, and compounds for allosteric modulation o

Details Methods, compositions, and compounds for allosteric modulation o Methods, compositions, and compounds for allosteric modulation o

1999-07-08

2000-11-07

Dees, Jose' G.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Cyclopentanohydrophenanthrene ring system doai

514172, 514176, 514177, 514178, 514179, 514180, 514181, 514182, 514816, 514817, 514818, 514899, 552600, 540106, 540107, 540108, 540110, A61K 3156, C07J 4100, C07J 500

Patent

active

061437360

ABSTRACT:
Methods, compositions, and compounds for modulating the GABA.sub.A receptor-chloride ionophore complex to alleviate stress, anxiety, seizures, mood disorders, PMS and PND and to induce anesthesia.

REFERENCES:
patent: 3274179 (1966-09-01), Christensen
patent: 3983111 (1976-09-01), Phillipps et al.
patent: 4898694 (1990-02-01), Schwartz et al.
patent: 5120723 (1992-06-01), Gee et al.
patent: 5208227 (1993-05-01), Gee et al.
patent: 5232917 (1993-08-01), Bolger et al.
patent: 5319115 (1994-06-01), Tahir et al.
patent: 5359054 (1994-10-01), Ottow et al.
patent: 5359055 (1994-10-01), Tsuji et al.
Aird, R.B. and Gordan, G.S., "Anticonvulsive Properties of Desoxycorticosterone," J. Amer. Med. Assoc. 145:715-719 (1951).
Arafat et al., "Sedative and hypnotic effects of oral administration of micronized progesterone may be mediated through its metabolites," Am. J. Obstet. Gynecol. 159:1203-1209 (1988).
Backstrom et al., "Endocrinological Aspects of Cyclical Mood Changes During the Menstrual Cycle or the Premenstrual Syndrome," J. Psychosom. Obstet. Gynaecol. 2:8-20 (1983).
Backstrom et al., "Ovarian Steroid Hormones--Effects on mood, behaviour and brain excitability," Acta Obstet. Gynecol. Scand. Suppl. 130:19-24 (1985).
Belelli et al., "Anticonvulsant Profile of the Progesterone Metabolite 5-.alpha.-pregnan-3-.alpha.-ol-20-one," Eur. J. Pharmacol. 166:325-329 (1989).
Bodor, N., "Novel Approaches in Prodrug Design," Drugs of the Future 6:165-182 (1981).
Callachan et al., "Modulation of the GABA.sub.A receptor by progesterone metabolites," Proc. R. Soc. Lond. B 231 359-369 (1987).
Conney et al., "Decreased Central Depressant Effect of Progesterone and other Steroids in Rats Pretreated with Drugs and Insecticides," J. Pharmacol. Exp. Ther. 154:310-318 (1966).
Dennerstein et al., "Progesterone and the premenstrual syndrome: a double blind crossover trial," British Med. J. 290:1617-1621 (1985).
Gee, K.W. and Yamamura, H.I., "Benzodiazepines and Barbiturates: Drugs for the Treatment of Anxiety, Insomnia, and Seizure Disorders," in: Drugs in Central Nervous System Disorders, D.C. Horwell, ed., pp. 123-147 (1985).
Gee et al., "GABA-Dependent Modulation of the Cl.sup.- Ionophore by Steroids in Rat Brain," Eur. J. Pharmacol. 136:419-423 (1987).
Gee et al., "Modulation of the Chloride Ionophore by Benzodiazepine Receptor Ligands: Influence of .gamma.-Aminobutyric Acid and Ligand Efficacy," Molec. Pharmacol. 30:218-225 (1986).
Gyermek, L., "Pregnanolone: A Highly Potent, Naturally Occurring Hypnotic-Anesthetic Agent," Proc. Soc. Exper. Biol. Med. 125:1058-1062 (1967).
Gyermek et al., "Structure-Activity Relationship of Some Steroidal Hypnotic Agents," J. Med. Chem. 11:117-125 (1968).
Harrison et al., "Structure-Activity Relationships for Steroid Interaction with the .gamma.-Aminobutyric Acid.sub.A Receptor Complex," J. Pharmacol. Exp. Ther. 241:346-353 (1987).
Horwell et al., "A Facile Method to Append Peptidal Side-Chains onto Steroidal Templates," Tetrahedron Lett. 50:4225-4234 (Mar. 1994).
Jacobsen et al., "Novel 21-aminosteroids that inhibit iron-dependent lipid peroxidation and protect against central nervous system trauma," J. Med. Chem. 33:1145-1151 (1990).
Laidlaw, J., "Catamenial Epilepsy," The Lancet, pp. 1235-1237 (Dec. 15, 1956).
Lambert et al., "Actions of synthetic and endogenous steroids on the GABA.sub.A receptor," Trends in Pharm. Sci. 8:224-227 (1987).
Lawrence et al., "Benzodiazepine Anticonvulsant Action: .gamma.-Aminobutyric Acid-Dependent Modulation of the Chloride Ionophore," Biochem. Biophys. Res. Comm. 123:1130-1137 (1984).
Lloyd, K.G. and Morselli, P.L., "Psychopharmacology of GABAergic Drugs," in: Psychopharmacology: The Third Generation of Progress, H.Y. Meltzer (ed.), Raven Press, NY, pp. 183-195 (1987).
Maddocks et al., "A Double-blind placebo-controlled trial of progesterone vaginal suppositories in the treatment of premenstrual syndrome," Am. J. Obstet. Gynecol. 154:573-581 (1986).
Majewska et al., "Steroids and Brain Activity. Essential Dialogue Between Body and Mind," Biochem. Pharmacol. 36:3781-3788 (1987).
Majewska et al., "Steroid Hormone Metabolites Are Barbiturate-Like Modulators of the GABA Receptor," Science 232:1004-1007 (1986).
Marker et al., "Isolation of epi-Pregnanol-3-one-20 from Human Pregnancy Urine," J. Amer. Chem. Soc. 59:616-618 (1937).
Mattson et al., "Medroxyprogesterone Therapy for Catamenial Epilepsy," Advances in Epileptology, vol. 15, Porter et al. (eds.), Washington, DC, Sep. 26-30, 1983, Raven Press, NY, pp. 279-282 (1984).
Mendelson et al., "Sleep induction by an adrenal steroid in the rat," Psychopharmacology 93:226-229 (1987).
Notari, R.E., "Theory and Practice of Prodrug Kinetics," Meth. Enzymol. 112:309-323 (1985).
Pfaff, D.W. and McEwen, B.S., "Actions of Estrogens and Progestins on Nerve Cells," Science 219:808-814 (1983).
Phillipps, G.H., "Structure-Activity Relationships in Steroidal Anaesthetics," Mol. Mech. Gen. Anaesth. Glaxo Symposium, pp. 32-47 (1974).
Phillipps, G.H., "Structure-Activity Relationships in Steroidal Anaesthetics," J. Steroid Biochem. 6:607-613 (1975).
Phillipps, G.H., "Water-Soluble Steroidal Anaesthetics," J. Steroid Biochem. 11:79-86 (1979).
Purdy et al., "Synthesis, Metabolism, and Pharmacological Activity of 3.alpha.-Hydroxy Steroids Which Potentiate GABA-Receptor-Mediated Chloride Ion Uptake in Rat Cerebral Cortical Synaptoneurosomes," J. Med. Chem. 33:1572-1581 (1990).
Raisinghani et al., "Uptake of Intravenously Administered Progesterone, Pregnanedione and Pregnanolone by the Rat Brain," Acta Endocrinologica 57:395-404 (1968).
Rosciszewska et al., "Ovarian hormones, anticonvulsant drugs, and seizures during the menstrual cycle in women with epilepsy," J. Neurol. Neurosurg. Psych. 49:47-51 (1986).
Squires et al., "[.sup.35 S]t-Butylbicyclophosphorothionate Binds with High Affinity to Brain-Specific Sites Coupled to .gamma.-Aminobutyric Acid-A and Ion Recognition Sites," Molec. Pharmacol. 23:326-336 (1983).
Swinyard, E.A. and Woodhead, J.H., "Experimental Detection, Quantification, and Evaluation of Anticonvulsants," in: Antileptic Drugs, Woodbury et al. (eds.), Raven Press, NY, pp. 111-126 (1982).
Wood et al., "In Vitro Characterization of Benzodiazepine Receptor Agonists, Antagonists, Inverse Agonists and Agonist/Antagonists," J. Pharmacol. Exp. Ther. 231:572-576 (1984).
Worms et al., ".gamma.-Aminobutyric Acid (GABA) Receptor Stimulation. I. Neuropharmacological Profiles of Progabide (SL 76002) and SL 75102, with Emphasis on their Anticonvulsant Spectra," J. Pharmacol. Exp. Ther. 220:660-671 (1982).
European Search Report for Application No. EP 95 91 3478, mailed Nov. 6, 1997.
Supplemental European Search Report for Application No. EP 95 91 3478, mailed Mar. 20, 1998.

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