Disclosed are methods for treating for treating congenital adrenal hyperplasia or primary aldosteronism in a subject in need thereof, comprising administering a therapeutically effective amount of 2S,4R ketoconazole enantiomer substantially free of the 2R,4S ketoconazole enantiomer to said subject. Also disclosed are compositions comprising a therapeutically effective amount of 2S,4R ketoconazole enantiomer substantially free of the 2R,4S ketoconazole enantiomer for use in treating a disease or condition associated with congenital adrenal hyperplasia or primary aldosteronism.

The present invention relates to RNAi agents, e.g., double-stranded RNAi agents, targeting the angiotensinogen (AGT) gene, and methods of using such RNAi agents to inhibit expression of AGT and methods of treating subjects having an AGT-associated disorder, e.g., hypertension.

Provided are a compound represented by the following formula (1):

##STR00001##

wherein X.sub.1 represents a hydrogen atom or a halogen atom, X.sub.2 represents a fluorine atom or a nitrile group, and X.sub.3 represents a radioactive halogen atom, or a salt thereof, and a medicament including the same.

The present invention relates to RNAi agents, e.g., double-stranded RNAi agents, targeting the angiotensinogen (AGT) gene, and methods of using such RNAi agents to inhibit expression of AGT and methods of treating subjects having an AGT-associated disorder, e.g., hypertension.

The present invention is directed to antibodies and fragments thereof having binding specificity for ACTH. Another embodiment of this invention relates to the antibodies binding fragments thereof described herein, comprising the sequences of the V.sub.H, V.sub.L and/or CDR polypeptides described herein, and the polynucleotides encoding them. The invention also contemplates conjugates of anti-ACTH antibodies and binding fragments thereof conjugated to one or more functional or detectable moieties. The invention further contemplates methods of making said anti-ACTH antibodies and binding fragments thereof. Embodiments of the invention also pertain to the use of anti-ACTH antibodies and binding fragments thereof for the diagnosis, assessment, prevention and treatment of diseases and disorders associated with ACTH, such as Cushing's Disease, Cushing's Syndrome, Parkinson's disease, obesity, diabetes, sleep disorders depression, anxiety disorders, cancer, muscle atrophy, hypertension, hyperinsulinemia, cognitive dysfunction, Alzheimer's disease, galactorrhea, stress related conditions, cardiac conditions, metabolic syndrome, hyperaldosteronism, Conn's syndrome and familial hyperaldosteronism.

The present invention is directed to antibodies and fragments thereof having binding specificity for ACTH. Embodiments of this invention relate to the binding fragments of antibodies described herein, comprising the sequences of the V.sub.H, V.sub.L and/or CDR polypeptides described herein, and the polynucleotides encoding them. The invention also contemplates anti-ACTH antibodies and binding fragments thereof conjugated to one or more functional or detectable moieties. The invention further contemplates methods of making said anti-ACTH antibodies and binding fragments thereof. Embodiments of the invention also pertain to the use of anti-ACTH antibodies and binding fragments thereof for the diagnosis, assessment, prevention and treatment of diseases and disorders associated with ACTH, such as CAH, FGD, Cushing's Disease, Cushing's Syndrome, Parkinson's disease, obesity, diabetes, sleep disorders, depression, anxiety disorders, cancer, muscle atrophy, hypertension, hyperinsulinemia, cognitive dysfunction, Alzheimer's disease, galactorrhea, stress related conditions, cardiac conditions, metabolic syndrome, hyperaldosteronism, Conn's syndrome and familial hyperaldosteronism.

Provided herein are methods for treating subjects having conditions related to adrenocortical activity and/or excessive steroid production. In particular, provided herein are methods for treating subjects having conditions related to adrenocortical activity and/or excessive steroid production through administration of at least one of the following agents: 1) an agent capable of inhibiting cholesterol efflux related to ABCA1 and/or ABCG1; 2) an agent capable of inhibiting MDR1 related cortisol secretion and/or MDR1 P-glycoprotein multiple drug transporter activity; and 3) an agent capable of inhibiting mitochondrial activity.

Provided herein are methods for treating subjects having conditions related to adrenocortical activity and/or excessive steroid production. In particular, provided herein are methods for treating subjects having conditions related to adrenocortical activity and/or excessive steroid production through administration of at least one of the following agents: 1) an agent capable of inhibiting cholesterol efflux related to ABCA1 and/or ABCG1; 2) an agent capable of inhibiting MDR1 related cortisol secretion and/or MDR1 P-glycoprotein multiple drug transporter activity; and 3) an agent capable of inhibiting mitochondrial activity.

The present invention provides a T-type calcium channel inhibitor which is a compound represented by formula (1), a pharmaceutically acceptable salt of this compound or a solvate of this compound. The present invention also provides: this T-type calcium channel inhibitor; a pharmaceutical product containing this T-type calcium channel inhibitor; and a therapeutic agent or prophylactic agent for diseases, the effective action of which is a T-type calcium channel inhibitory action. (In formula (1), each of R.sup.1 and R.sup.2 independently represents H, OH or OR.sup.11 wherein R.sup.11 represents a C.sub.1-3 alkyl group; each of R.sup.3 and R.sup.4 independently represents H, OH or OR.sup.12, wherein R.sup.12 represents a C.sub.1-3 alkyl group; and each of R.sup.5 and R.sup.6 independently represents H, a halogen atom, a C.sub.1-10 alkyl group, a C.sub.2-6 alkenyl group, a C.sub.2-6 alkynyl group, a phenyl group (which may be substituted by a C.sub.1-6 alkoxy group or a halogen atom), a C.sub.1-3 alkyl-phenyl group (which may be substituted by a C.sub.1-6 alkyloxy group or a halogen atom) or a C.sub.10-50 prenyl group.) ##STR00001##

The invention relates to glucocorticoid replacement therapy and provides pharmaceutical compositions and kits designed to deliver one or more glucocorticoids to a subject in need thereon in a manner that results in serum levels of the glucocorticoid that essentially mimic that of a healthy subject for a clinically relevant period of time. The pharmaceutical compositions and kits are prepared in such a way that a first part of one or more glucocorticoids is substantially immediately released and a second part of one or more glucocorticoids is released over an extended period of time of at least about 8 hours. The invention also relates to a method for treating diseases requiring glucocorticoid treatment such as in subjects having a glucocorticoid deficiency disorder.