Pramipexole (
Mirapex,
Mirapexin,
Sifrol) is a
medicationA pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
indicated for treating
Parkinson's diseaseParkinson's disease is a degenerative disorder of the central nervous system that often impairs the sufferer's motor skills, speech, and other functions....
and
restless legs syndromeRestless legs syndrome , also known as Wittmaack-Ekbom's syndrome, is a condition that is characterized by an irresistible urge to move one's body to stop uncomfortable or odd sensations. It most commonly affects the legs, but can also affect the arms or torso and even phantom limbs. Moving the...
(RLS). It is also sometimes used
off-labelOff-label use is the practice of prescribing pharmaceuticals for an unapproved indication.. In the United States, the Food and Drug Administration Center for Drug Evaluation and Research reviews a company's New Drug Application for data from clinical trials to see if the results support the drug...
as a treatment for
cluster headacheCluster headache, nicknamed "suicide headache", is a neurological disease that involves, as its most prominent feature, an immense degree of pain. "Cluster" refers to the tendency of these headaches to occur periodically, with active periods interrupted by spontaneous remissions. The cause of the...
and to counteract the problems with
sexual dysfunctionSexual dysfunction or sexual malfunction refers to a difficulty experienced by an individual or a couple during any stage of a normal sexual activity, including desire, arousal or orgasm.-Categories:...
experienced by some users of the
selective serotonin reuptake inhibitor Selective serotonin reuptake inhibitors or serotonin-specific reuptake inhibitor are a class of compounds typically used as antidepressants in the treatment of depression, anxiety disorders, and some personality disorders...
(SSRI)
antidepressantAn antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia. Drugs including the monoamine oxidase inhibitors , tricyclic antidepressants , tetracyclic antidepressants , selective serotonin reuptake inhibitors , and serotonin-norepinephrine...
s. Pramipexole has shown robust effects on pilot studies in a placebo-controlled proof of concept study in
bipolar disorderBipolar disorder, also known as manic depressive disorder, manic depression or bipolar affective disorder, is a serious mental disorder that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated mood clinically referred to as mania or, if...
. It is also being investigated for the treatment of
clinical depressionMajor depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and loss of interest or pleasure in normally enjoyable activities...
and
fibromyalgiaFibromyalgia is also referred to as FM or FMS. Fibromyalgia is characterized by chronic widespread pain and also allodynia, a heightened and painful response to pressure...
.
Pramipexole acts as a selective non-
ergolineErgoline is a chemical compound whose structural skeleton is contained in a diverse range of alkaloids including a few psychedelic drugs...
D2Dopamine receptor D2, also known as D2R, is a protein which in humans is encoded by the DRD2 gene.- Function :This gene encodes the D2 subtype of the dopamine receptor. This G-protein coupled receptor inhibits adenylyl cyclase activity...
,
D3D dopamine receptor is a protein that in humans is encoded by the DRD3 gene.This gene encodes the D
3 subtype of the dopamine receptor. The D
3 subtype inhibits adenylyl cyclase through inhibitory G-proteins...
, and D
4 dopamineDopamine is a neurotransmitter occurring in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this phenethylamine functions as a neurotransmitter, activating the five types of dopamine receptors — D
1, D
2, D
3, D
4, and...
receptorReceptor may refer to:*Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse...
full agonist (see
dopamine agonistA dopamine agonist is a compound that activates dopamine receptors in the absence of the dopamine ligand. Dopamine agonists activate signaling pathways through the dopamine receptor and trimeric G-proteins ultimately leading to changes in gene transcription....
) with highest
affinityIn chemical physics and physical chemistry, chemical affinity can be defined as electronic properties by which dissimilar chemical species are capable of forming chemical compounds...
by 5-fold for D
3.
Parkinson's disease is a
neurodegenerative diseaseNeurodegenerative disease is a condition in which cells of the brain and spinal cord are lost. The brain and spinal cord are composed of neurons that perform different functions such as controlling movements, processing sensory information, and making decisions...
affecting the
substantia nigraThe substantia nigra is a brain structure located in the mesencephalon that plays an important role in reward, addiction, and movement. Substantia nigra is Latin for "black substance", as parts of the substantia nigra appear darker than neighboring areas due to high levels of melanin in...
, a component of the
basal gangliaThe basal ganglia are a group of nuclei in the brains of vertebrates, situated at the base of the forebrain and strongly connected with the cerebral cortex, thalamus and other areas. The basal ganglia are associated with a variety of functions, including motor control and learning...
.
Pramipexole (
Mirapex,
Mirapexin,
Sifrol) is a
medicationA pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
indicated for treating
Parkinson's diseaseParkinson's disease is a degenerative disorder of the central nervous system that often impairs the sufferer's motor skills, speech, and other functions....
and
restless legs syndromeRestless legs syndrome , also known as Wittmaack-Ekbom's syndrome, is a condition that is characterized by an irresistible urge to move one's body to stop uncomfortable or odd sensations. It most commonly affects the legs, but can also affect the arms or torso and even phantom limbs. Moving the...
(RLS). It is also sometimes used
off-labelOff-label use is the practice of prescribing pharmaceuticals for an unapproved indication.. In the United States, the Food and Drug Administration Center for Drug Evaluation and Research reviews a company's New Drug Application for data from clinical trials to see if the results support the drug...
as a treatment for
cluster headacheCluster headache, nicknamed "suicide headache", is a neurological disease that involves, as its most prominent feature, an immense degree of pain. "Cluster" refers to the tendency of these headaches to occur periodically, with active periods interrupted by spontaneous remissions. The cause of the...
and to counteract the problems with
sexual dysfunctionSexual dysfunction or sexual malfunction refers to a difficulty experienced by an individual or a couple during any stage of a normal sexual activity, including desire, arousal or orgasm.-Categories:...
experienced by some users of the
selective serotonin reuptake inhibitor Selective serotonin reuptake inhibitors or serotonin-specific reuptake inhibitor are a class of compounds typically used as antidepressants in the treatment of depression, anxiety disorders, and some personality disorders...
(SSRI)
antidepressantAn antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia. Drugs including the monoamine oxidase inhibitors , tricyclic antidepressants , tetracyclic antidepressants , selective serotonin reuptake inhibitors , and serotonin-norepinephrine...
s. Pramipexole has shown robust effects on pilot studies in a placebo-controlled proof of concept study in
bipolar disorderBipolar disorder, also known as manic depressive disorder, manic depression or bipolar affective disorder, is a serious mental disorder that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated mood clinically referred to as mania or, if...
. It is also being investigated for the treatment of
clinical depressionMajor depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and loss of interest or pleasure in normally enjoyable activities...
and
fibromyalgiaFibromyalgia is also referred to as FM or FMS. Fibromyalgia is characterized by chronic widespread pain and also allodynia, a heightened and painful response to pressure...
.
Pharmacology
Pramipexole acts as a selective non-
ergolineErgoline is a chemical compound whose structural skeleton is contained in a diverse range of alkaloids including a few psychedelic drugs...
D2Dopamine receptor D2, also known as D2R, is a protein which in humans is encoded by the DRD2 gene.- Function :This gene encodes the D2 subtype of the dopamine receptor. This G-protein coupled receptor inhibits adenylyl cyclase activity...
,
D3D dopamine receptor is a protein that in humans is encoded by the DRD3 gene.This gene encodes the D
3 subtype of the dopamine receptor. The D
3 subtype inhibits adenylyl cyclase through inhibitory G-proteins...
, and D
4 dopamineDopamine is a neurotransmitter occurring in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this phenethylamine functions as a neurotransmitter, activating the five types of dopamine receptors — D
1, D
2, D
3, D
4, and...
receptorReceptor may refer to:*Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse...
full agonist (see
dopamine agonistA dopamine agonist is a compound that activates dopamine receptors in the absence of the dopamine ligand. Dopamine agonists activate signaling pathways through the dopamine receptor and trimeric G-proteins ultimately leading to changes in gene transcription....
) with highest
affinityIn chemical physics and physical chemistry, chemical affinity can be defined as electronic properties by which dissimilar chemical species are capable of forming chemical compounds...
by 5-fold for D
3.
Parkinson's disease is a
neurodegenerative diseaseNeurodegenerative disease is a condition in which cells of the brain and spinal cord are lost. The brain and spinal cord are composed of neurons that perform different functions such as controlling movements, processing sensory information, and making decisions...
affecting the
substantia nigraThe substantia nigra is a brain structure located in the mesencephalon that plays an important role in reward, addiction, and movement. Substantia nigra is Latin for "black substance", as parts of the substantia nigra appear darker than neighboring areas due to high levels of melanin in...
, a component of the
basal gangliaThe basal ganglia are a group of nuclei in the brains of vertebrates, situated at the base of the forebrain and strongly connected with the cerebral cortex, thalamus and other areas. The basal ganglia are associated with a variety of functions, including motor control and learning...
. The substantia nigra has a high quantity of
dopaminergicDopaminergic means related to the neurotransmitter dopamine. For example, certain proteins such as the dopamine transporter , vesicular monoamine transporter 2 , and dopamine receptors can be classified as dopaminergic, and neurons which synthesize or contain dopamine and synapses with dopamine...
neuronA neuron is an excitable cell in the nervous system that processes and transmits information by electrochemical signaling. Neurons are the core components of the brain, the vertebrate spinal cord, the invertebrate ventral nerve cord, and the peripheral nerves...
s, which are
nerveA nerve is an enclosed, cable-like bundle of peripheral axons . A nerve provides a common pathway for the electrochemical nerve impulses that are transmitted along each of the axons. Nerves are found only in the peripheral nervous system...
cellsThe cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of an organism that is classified as living, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos...
that release the
neurotransmitterNeurotransmitters are endogenous chemicals which relay, amplify, and modulate signals between a neuron and another cell. Neurotransmitters are packaged into synaptic vesicles that cluster beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they...
known as
dopamineDopamine is a neurotransmitter occurring in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this phenethylamine functions as a neurotransmitter, activating the five types of dopamine receptors — D
1, D
2, D
3, D
4, and...
. When dopamine is released, it may activate
dopamine receptorDopamine receptors are a class of metabotropic G protein-coupled receptors that are prominent in the vertebrate central nervous system . The neurotransmitter dopamine is the primary endogenous ligand for dopamine receptors....
s in the
striatumThe striatum also known as striate body or striate nucleus is a subcortical part of the telencephalon/cerebrum. It is the major input station of the basal ganglia system...
, which is another component of the basal ganglia. When neurons of the substantia nigra deteriorate in Parkinson's disease, the striatum no longer properly receives dopamine signals. As a result, the basal ganglia can no longer regulate body movement effectively and motor function becomes impaired.
By acting as an agonist for the D
2, D
3, and D
4 dopamine receptors, pramipexole may directly stimulate the underfunctioning dopamine receptors in the
striatumThe striatum also known as striate body or striate nucleus is a subcortical part of the telencephalon/cerebrum. It is the major input station of the basal ganglia system...
, thereby restoring the dopamine signals needed for proper functioning of the basal ganglia.
Adverse effects
Some of the more common side effects of pramipexole include:
- Changes in appetite and weight
- Dizziness, lightheadedness, or fainting, especially when standing up (orthostatic hypotension
Orthostatic hypotension is a form of hypotension in which a person's blood pressure suddenly falls when the person stands up...
)
- Drowsiness
- Hallucination
A hallucination, in the broadest sense, is a perception in the absence of a stimulus. In a stricter sense, hallucinations are defined as perceptions in a conscious and awake state in the absence of external stimuli which have qualities of real perception, in that they are vivid, substantial, and...
s (seeing, hearing, or feeling things that are not there)
- Nausea
Nausea is the sensation of unease and discomfort in the stomach with an urge to vomit.-Causes:...
- Insomnia
Insomnia is a symptom of any of several sleep disorders, characterized by persistent difficulty falling asleep or staying asleep despite the opportunity. Insomnia is a symptom, not a stand-alone diagnosis or a disease. By definition, insomnia is "difficulty initiating or maintaining sleep, or both"...
- Twitching, twisting, or other unusual body movements
- Unusual tiredness or weakness
Several unusual adverse effects of pramipexole (and related D
3-preferring dopamine agonist medications such as
ropiniroleRopinirole is a non-ergoline dopamine agonist. It is manufactured by GlaxoSmithKline and Sun Pharmaceutical. It is used in the treatment of Parkinson's disease...
) may include
compulsive gamblingProblem gambling is an urge to gamble despite harmful negative consequences or a desire to stop. The term is preferred to compulsive gambling among many professionals, as few people described by the term experience true compulsions in the clinical sense of the word...
,
hypersexualityHypersexuality is the desire to engage in human sexual behavior at a level high enough to be considered clinically significant.-Concept:The concept of hypersexuality replaces the older concepts of nymphomania and satyriasis...
, and
overeatingOvereating generally refers to the long-term consumption of excess food in relation to the energy that an organism expends , leading to weight gain and often obesity. It may be regarded as an eating disorder....
, even in patients without any prior history of these behaviours. Other compulsive behaviors, such as excessive shopping and even cross-dressing, have been reported. These side effects are thought to be linked to the D
3 activity of pramipexole, as D
3 receptors are heavily expressed in brain regions involved in mood, behavior, and reward.
External links