Novel compounds having a D3 receptor antagonistic effect are provided. The compound represented by Formula (IA)′: ##STR00001##
wherein A is S or O; R.sup.1a is substituted or unsubstituted alkyloxy or the like, R.sup.2a to R.sup.2d are each independently hydrogen atoms or the like, ring B is a 4- to 8-membered non-aromatic carbocycle or the like, R.sup.3 is each independently halogen or the like, r is an integer of 0 to 4, R.sup.4 is substituted or unsubstituted aromatic heterocyclyl or the like,
or a pharmaceutically acceptable salt thereof.

This invention is in the field of medicinal chemistry. In particular, the invention relates to anew class of small-molecules having a tetrahydroindazole structure which function as modulators (e.g., activators or inhibitors) of sigma-1 and/or sigma-2 receptors, and their use as therapeutics for the treatment of cancer and other diseases (e.g., neurological conditions) characterized with sigma-1 and/or sigma-2 receptor activity.

The present invention provides formulations comprising: L-threonine; Glycine; L-phenylalanine; DL-phenylalanine; Glutamine; NAD; and Magnesium, for use in the treatment of different types of addictions, such as: psychotropic medications, illicit drugs, tobacco and alcohol including, for example, but not limited to, narcotics, benzodiazepines, marijuana, cocaine, methamphetamines, antidepressants, and antipsychotics. The formulations of the present invention promote a detoxification process which facilitates that the brain repairs the damage caused by the abuse of addictive substances.

The present invention provides formulations comprising: L-threonine; Glycine; L-phenylalanine; DL-phenylalanine; Glutamine; NAD; and Magnesium, for use in the treatment of different types of addictions, such as: psychotropic medications, illicit drugs, tobacco and alcohol including, for example, but not limited to, narcotics, benzodiazepines, marijuana, cocaine, methamphetamines, antidepressants, and antipsychotics. The formulations of the present invention promote a detoxification process which facilitates that the brain repairs the damage caused by the abuse of addictive substances.

A method of treating a patient with a psychedelic, by administering either a dose of LSD to the patient that is equivalent to a known dose of psilocybin with desired acute and therapeutic effects, or administering a dose of psilocybin to the patient that is equivalent to a known dose of LSD with desired acute and therapeutic effects. A method of treating a patient with LSD, by administering a dose of LSD to the patient equivalent to those of psilocybin known to be associated with positive long-term therapeutic outcomes. A method of determining a dose of a psychedelic or the dose-equivalence to another psychedelic to be administered to an individual, by administering a dose of a psychedelic to an individual, determining positive acute effects and negative acute effects in the individual, and adjusting the dose to provide more positive acute effects than negative acute effects in the individual.

The invention relates to a derivative of a GLP-1 analogue of a general Formula I, which derivative comprises a side chain attached to a Lys residue at position 34, 35, 36, 37, or 38 of the GLP-1 analogue, which side chain comprises a Branched linker, a 1.sup.st and a 2.sup.nd Protractor selected from C18 diacid, C20 diacid, and sulfonic acid C16, and at least one Linker element-1 incorporating ethylene glycol units. Linker element-1 may be incorporated in an optional Pre-linker, and/or in a 1.sup.st or 2.sup.nd Post-linker. The invention also relates to novel GLP-1 analogues, novel side chain intermediate products and their manufacture and use to prepare derivatives of biologically active peptides and proteins, as well as pharmaceutical compositions and medical uses of the analogues and derivatives. The derivatives have very long half-lives while maintaining a satisfactory potency, which makes them potentially suitable for once-monthly administration.

Provided herein are nanoparticle conjugated synthetic opioid prodrugs that target the peripheral mu opioid receptor (MOR). The prodrugs exhibit long-lived bioavailability, do not compromise the analgesic effects of opioids administered for pain relief (and in some cases can be used for pain relief), and do not induce opioid withdrawal symptoms, when their use is discontinued. Certain of the prodrugs are especially useful for the prevention and/or treatment of unwanted opioid-induced side effects such as opioid-induced constipation (OIC).

The invention provides novel, multiply-substituted 1-aryl-3-azabicyclo[3.1.0]hexanes, and related processes and intermediates for preparing these compounds, as well as compositions and methods employing these compounds for the treatment and/or prevention of central nervous system (CNS) disorders, including depression and anxiety.

A method for treating conditions associated with thalamocortical dysrhythmia. The method includes applying transcranial low voltage electrical stimulation (TLVES) therapy or transcranial magnetic stimulation (TMS) therapy to a patient in need thereof, and administering to the patient a dissociative anesthetic during the TLVES therapy or the TMS therapy. A number of conditions including tinnitus, depression and pain can be treated with TLVES or TMS in combination with the dissociative anesthetic, such as an NMADR inhibitor, including ketamine.

The present invention concerns a dosage form comprising oxycodone and naloxone which is characterized by specific in vivo parameters such as t.sub.max, C.sub.max, AUCt value, mean bowel function score and/or duration of analgesic efficacy.