Background of Dopamine and Its Receptors
In 1957, the Swedish scientist Arvid Carlsson first discovered dopamine and proposed that dopamine is not only a precursor of norepinephrine, it is also a neurotransmitter located in the brain. Arvid Carlsson woned the Nobel Prize in Physiology and Medicine in 2000 after 43 years. People have now understood and realized that dopamine is universally present in the nervous system of humans and animals. It is a catecholamine neurotransmitter and plays a very important role in the generation and transmission of pleasant sensations and the storage of pleasant information. In addition, dopamine is also associated with various addictive behaviors. Catecholamine is a neurological substance containing catechol and amine groups. Generally, catecholamines refer to norepinephrine (NA), adrenaline (ADR) and dopamine (DA).
Dopamine Pathways
There are 4 dopamine pathways in the mammalian central nervous system:
1. Nigrostriatal pathway: starting from the substantia nigra of the midbrain and ending in the striatum;
2. The mesolimbic pathway: starting from the midbrain and projecting to the nucleus accumbens located in the ventral striatum;
3. The mesocortical pathway: also starts from the ventral brainstem, but projects to the frontal cortex;
4. The tuberoinfundibular pathway: This pathway projects from hypothalamic DA neurons to the adenohypophysis.
Type of Dopamine Receptors
For dopamine to work, it must bind to the corresponding receptors. Dopamine receptors belong to the family of G protein-coupled receptors. According to the different binding ability of the receptor to the ligand, dopamine receptors are divided into 5 subtypes, and then according to their biochemical and pharmacological properties, they can be divided into D1 and D2 receptors. D1 receptors include D1 and D5 receptors, which increase the level of intracellular cAMP after activation. D2 receptors include D2, D3 and D4 receptors, which can reduce cAMP levels in the cell after activation.
Distribution of Dopamine Receptors
D1 receptors are the most distributed dopamine receptors in the forebrain of mammals, mainly in the striatum, nucleus accumbens and olfactory nodules. D5 receptors are mainly distributed in the hippocampus and hypothalamus, and their concentration and distribution are very small compared with D1 receptors. Dopamine D2 receptor is the second most abundant receptor subtype in the mammalian forebrain of the dopamine receptor family. It is mainly distributed in the striatum, nucleus accumbens, olfactory nodules and substantia nigra. Studies have found that most anti-Parkinson and antipsychotic drugs act on D2-like receptors (D2, D3, and D4). D2 receptors are also closely related to the addictive nature of drugs and alcohol. D3 receptors are mainly distributed in the limbic system, and D4 receptors are distributed in the pyramidal and non-pyramidal neurons of the cerebral cortex and hippocampus.
FDA approved dopamine receptors agonist used to treat Disease
Pramipexole Dihydrochloride: A dopamine receptor agonist exhibiting selectivity for the D3 receptor. It used to treat the signs and symptoms of idiopathic Parkinson’s disease and Restless Legs Syndrome (RLS).
Ropinirole Hydrochloride: The hydrochloride salt form of ropinirole, a non-ergot dopamine receptors agonist with antiparkinsonian property.
Rotigotine: A non-selective dopamine receptor agonist used for the treatment of Parkinson’s Disease and Restless Leg Syndrome.
Risperidone: A second-generation antipsychotic medication used to treat a number of mental health disorders including schizophrenia, bipolar mania, psychosis, or as an adjunct in severe depression.
Paliperidone: An atypical antipsychotic used in the treatment of schizophrenia and other schizoaffective or delusional disorders.
Olanzapine: An antipsychotic drug used in the management of schizophrenia, bipolar 1 disorder, and agitation associated with these disorders.
Aripiprazole: An atypical antipsychotic used in the treatment of a wide variety of mood and psychotic disorders, such as schizophrenia, bipolar I, major depressive disorder, irritability associated with autism, and Tourette’s syndrome.
| Name | Phase | Disease | Dopamine Receptors |
| RP-5063 | 3 | Schizophrenia | Dopamine D2/D3/D4 Receptor Agonist |
| FKF02SC | 2 | Schizophrenia | Dopamine D1/D2/D3/D4 Receptor Antagonist |
| F-17464 | 2 | Schizophrenia | Dopamine D3 Receptor Antagonist |
| ITI-214 | 2 | Parkinson’s disease | Dopamine D1 Receptor Agonist |
| Aplindore | 2 | Parkinson’s disease/RLS | Dopamine D2/D3 Receptor Agonist |
| Ecopipam | 3 | Lesch-Nyhan syndrome | Dopamine D1/D5 Receptor Antagonist |
| Apomorphine Hydrochloride | 2 | Traumatic Brain Injury | Dopamine D1/D2 Receptor Agonist |
Summary
The discovery of dopamine, a mysterious substance that can make people feel pleasurable in the human brain, has profoundly affected the development of modern neurology. Based on the research on dopamine and its receptors, it currently includes multiple treatments of dopamine receptor agonists and antagonists.