Antalarmin
Encyclopedia
Antalarmin is a drug that acts as a CRF-1
antagonist.
Corticotropin-releasing factor (CRF), also known as Corticotropin-releasing hormone
, is an endogenous peptide hormone released in response to various triggers such as chronic stress and drug addiction. This, then, triggers the release of corticotropin
(ACTH), another hormone involved in the physiological response to stress. Chronic release of CRF and ACTH is believed to be directly or indirectly involved in many of the harmful physiological effects of chronic stress, such as excessive glucocorticoid
release, stomach ulcers
, anxiety
, diabetes mellitus
, osteoporosis
, depression
, and development of high blood pressure
and consequent cardiovascular problems.
Antalarmin is a non-peptide drug that blocks the CRF-1 receptor, and, as a consequence, reduces the release of ACTH in response to chronic stress. This has been demonstrated in animals to reduce the behavioural responses to stressful situations, and it is proposed that antalarmin itself, or more likely newer CRF antagonist drugs still under development, could be useful for reducing the adverse health consequences of chronic stress in humans, as well as having possible uses in the treatment of conditions such as anxiety, depression, and drug addiction.
Results so far have had limited success, with various CRF antagonists being tested, which showed some antidepressant effects, but failed to produce an effect comparable with conventional antidepressant drugs. However more positive results were seen when antalarmin was combined with an SSRI antidepressant, suggesting a potential for synergistic effect. Encouraging results have also been observed using antalarmin as a potential treatment for anxiety and stress-induced hypertension.
Chronic antalarmin treatment also showed anti-inflammatory effects and has been suggested as having potential uses in the treatment of inflammatory conditions such as arthritis
, as well as stress-induced gastrointestinal ulcers and irritable bowel syndrome
.
Mixed results have been seen in research into the use of antalarmin and other CRF-1 antagonists in the treatment of drug addiction disorders. Tests of antalarmin on cocaine use in cocaine-addicted monkeys produced only slight reductions of use that were not statistically significant, however in tests on cocaine-addicted rats, antalarmin did prevent dose escalation with prolonged use, suggesting that it might stabilise cocaine use and prevent it increasing over time, although without consistently reducing it.
Antalarmin also showed positive effects in reducing withdrawal syndrome from chronic opioid use, and significantly reduced self-administration of ethanol in ethanol-addicted rodents.
Corticotropin releasing hormone receptor 1
Corticotropin releasing hormone receptor 1 is a protein, also known as CRF1, with the latter now being the IUPHAR-recommended name...
antagonist.
Corticotropin-releasing factor (CRF), also known as Corticotropin-releasing hormone
Corticotropin-releasing hormone
Corticotropin-releasing hormone , originally named corticotropin-releasing factor , and also called corticoliberin, is a polypeptide hormone and neurotransmitter involved in the stress response...
, is an endogenous peptide hormone released in response to various triggers such as chronic stress and drug addiction. This, then, triggers the release of corticotropin
Adrenocorticotropic hormone
Adrenocorticotropic hormone , also known as 'corticotropin', 'Adrenocorticotrophic hormone', is a polypeptide tropic hormone produced and secreted by the anterior pituitary gland. It is an important component of the hypothalamic-pituitary-adrenal axis and is often produced in response to biological...
(ACTH), another hormone involved in the physiological response to stress. Chronic release of CRF and ACTH is believed to be directly or indirectly involved in many of the harmful physiological effects of chronic stress, such as excessive glucocorticoid
Glucocorticoid
Glucocorticoids are a class of steroid hormones that bind to the glucocorticoid receptor , which is present in almost every vertebrate animal cell...
release, stomach ulcers
Peptic ulcer
A peptic ulcer, also known as PUD or peptic ulcer disease, is the most common ulcer of an area of the gastrointestinal tract that is usually acidic and thus extremely painful. It is defined as mucosal erosions equal to or greater than 0.5 cm...
, anxiety
Anxiety
Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...
, diabetes mellitus
Diabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
, osteoporosis
Osteoporosis
Osteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered...
, depression
Depression (mood)
Depression is a state of low mood and aversion to activity that can affect a person's thoughts, behaviour, feelings and physical well-being. Depressed people may feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable, or restless...
, and development of high blood pressure
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
and consequent cardiovascular problems.
Antalarmin is a non-peptide drug that blocks the CRF-1 receptor, and, as a consequence, reduces the release of ACTH in response to chronic stress. This has been demonstrated in animals to reduce the behavioural responses to stressful situations, and it is proposed that antalarmin itself, or more likely newer CRF antagonist drugs still under development, could be useful for reducing the adverse health consequences of chronic stress in humans, as well as having possible uses in the treatment of conditions such as anxiety, depression, and drug addiction.
Results so far have had limited success, with various CRF antagonists being tested, which showed some antidepressant effects, but failed to produce an effect comparable with conventional antidepressant drugs. However more positive results were seen when antalarmin was combined with an SSRI antidepressant, suggesting a potential for synergistic effect. Encouraging results have also been observed using antalarmin as a potential treatment for anxiety and stress-induced hypertension.
Chronic antalarmin treatment also showed anti-inflammatory effects and has been suggested as having potential uses in the treatment of inflammatory conditions such as arthritis
Arthritis
Arthritis is a form of joint disorder that involves inflammation of one or more joints....
, as well as stress-induced gastrointestinal ulcers and irritable bowel syndrome
Irritable bowel syndrome
Irritable bowel syndrome is a diagnosis of exclusion. It is a functional bowel disorder characterized by chronic abdominal pain, discomfort, bloating, and alteration of bowel habits in the absence of any detectable organic cause. In some cases, the symptoms are relieved by bowel movements...
.
Mixed results have been seen in research into the use of antalarmin and other CRF-1 antagonists in the treatment of drug addiction disorders. Tests of antalarmin on cocaine use in cocaine-addicted monkeys produced only slight reductions of use that were not statistically significant, however in tests on cocaine-addicted rats, antalarmin did prevent dose escalation with prolonged use, suggesting that it might stabilise cocaine use and prevent it increasing over time, although without consistently reducing it.
Antalarmin also showed positive effects in reducing withdrawal syndrome from chronic opioid use, and significantly reduced self-administration of ethanol in ethanol-addicted rodents.