According to the invention there is provided a compound of formula A1 which may be useful in the treatment of a condition or disorder ameliorated by the inhibition of the A.sub.1-A.sub.2b or, particularly, the A.sub.2a receptor wherein the compound of formula A1 has the structure, wherein, A represents Cy.sup.1 or Het.sup.A; Cy.sup.1 represents a 5- to 14-membered aromatic, fully saturated or partially unsaturated carbocyclic ring system comprising one, two or three rings, which Cy.sup.1 group is optionally substituted by one or more R.sup.4a substituents; Het.sup.A represents a 5- to 14-membered heterocyclic group that may be aromatic, fully saturated or partially unsaturated, and which contains one or more hetermatoms selected from O, S and N, which heterocyclic group may comprise one, two or three rings and which HetA group is optionally substituted by one or more R4b substituents; B represents a Cy.sup.2 or Het.sup.B; Cy.sup.2 represents a 3- to 10-membered aromatic, fully saturated or partially unsaturated carbocyclic ring system comprising one or two rings, which Cy.sup.2 group is optionally substituted by one or more R.sup.4c substituents; Het.sup.B represents a 3- to 10-membered heterocyclic group that may be aromatic, fully saturated or partially unsaturated, and which contains one or more heteroatoms selected from O, S and N, which heterocyclic group may comprise one or two rings and which Het.sup.B group is optionally substituted by one or more R.sup.4d substituents.

##STR00001##

Disclosed herein are tricyclic compounds, including pyrimido[4′,5′:4,5]thieno[2,3-c]pyridazine-8-amine, pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidine-4-amine, pyrazino[2′,3′:4,5]thieno[3,2-d]pyrimidin-4-amine, pyrido[3′,2′:4,5]furo[3,2-d]pyrimidin-4-amine, and pyrimido[4′,5′:4,5]furo[2,3-c]pyridazin-8-amine compounds, which may be useful as positive allosteric modulators of the muscarinic acetylcholine receptor M.sub.4 (mAChR M.sub.4). Also disclosed herein are methods of making the compounds, pharmaceutical compositions comprising the compounds, and methods of treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction using the compounds and compositions.

A composition for modulating intestinal permeability and/or treating and/or preventing leaky gut related diseases including a Chinese herbal compound material or a Chinese herbal compound extract is provided. The Chinese herbal compound material includes Ganoderma, red jujube, longan and lotus seed. Moreover, the Chinese herbal compound extract includes a Ganoderma extract, a red jujube extract, a longan extract and a lotus seed extract.

A composition for modulating intestinal permeability and/or treating and/or preventing leaky gut related diseases including a Chinese herbal compound material or a Chinese herbal compound extract is provided. The Chinese herbal compound material includes Ganoderma, red jujube, longan and lotus seed. Moreover, the Chinese herbal compound extract includes a Ganoderma extract, a red jujube extract, a longan extract and a lotus seed extract.

The present invention relates to a composition for preventing sleep disorders or insomnia, containing an enzyme-treated Ashwagandha extract as an active ingredient, and specifically, since it was confirmed that in an animal model and a sleep disorder animal model, which were administered an enzyme-treated Ashwagandha extract, sleep latency and awake time during sleep were decreased, sleep time, non-rapid eye movement (NREM) sleep time and δ-waves were increased, and as a result, sleep activity was improved, the enzyme-treated Ashwagandha extract can be used as an active ingredient of a composition for preventing or treating sleep disorders or insomnia.

The present invention relates to a composition for preventing sleep disorders or insomnia, containing an enzyme-treated Ashwagandha extract as an active ingredient, and specifically, since it was confirmed that in an animal model and a sleep disorder animal model, which were administered an enzyme-treated Ashwagandha extract, sleep latency and awake time during sleep were decreased, sleep time, non-rapid eye movement (NREM) sleep time and δ-waves were increased, and as a result, sleep activity was improved, the enzyme-treated Ashwagandha extract can be used as an active ingredient of a composition for preventing or treating sleep disorders or insomnia.

Compounds that selectively negatively modulate NMDA receptors containing an NR1/NR2B subunit, pharmaceutical compositions comprising the compounds, and methods of treating a disease using the compounds are disclosed.

The invention relates to compounds of formula ##STR00001##
wherein R, R.sup.1, R.sup.2, X, and Y are as defined herein and to a pharmaceutically suitable acid addition salt thereof. Compounds of formula I have a good affinity to the trace amine associated receptors (TAARs), especially for TAAR1. The compounds can be used for the treatment of depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder (ADHD), stress-related disorders, psychotic disorders such as schizophrenia, neurological diseases such as Parkinson's disease, neurodegenerative disorders such as Alzheimer's disease, epilepsy, migraine, hypertension, substance abuse and metabolic disorders such as eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders.

Stress is any demand placed on the brain or physical body, thereby leading to anxiety and depression and it is a common phenomenon experienced by humans and animals. Stress, anxiety and depression often leads to serious mental ill health. People with anxiety disorders respond to certain things or situations with fear and dread and display physical signs such as a pounding heart and sweating. Often, people lose their willpower, concentration and interest in day to day activities, are drained of energy and can even become devoid of any emotion.

It is documented that low activity of certain neurotransmitters can result in anxiety, chronic stress, depression, difficulty in concentrating, memory problems, muscle pain, headaches, insomnia and sleep problems. Therefore, if the level of these neurotransmitters is raised, the problem of stress, anxiety and depression can be cured. The invention describes a formulation to naturally increase the levels of certain neurotransmitters in the body, thereby reducing stress, anxiety and depression.

Stress is any demand placed on the brain or physical body, thereby leading to anxiety and depression and it is a common phenomenon experienced by humans and animals. Stress, anxiety and depression often leads to serious mental ill health. People with anxiety disorders respond to certain things or situations with fear and dread and display physical signs such as a pounding heart and sweating. Often, people lose their willpower, concentration and interest in day to day activities, are drained of energy and can even become devoid of any emotion.

It is documented that low activity of certain neurotransmitters can result in anxiety, chronic stress, depression, difficulty in concentrating, memory problems, muscle pain, headaches, insomnia and sleep problems. Therefore, if the level of these neurotransmitters is raised, the problem of stress, anxiety and depression can be cured. The invention describes a formulation to naturally increase the levels of certain neurotransmitters in the body, thereby reducing stress, anxiety and depression.