A
dopamine reuptake inhibitor (
DRI,
DARI) is a type of
drugA drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...
which acts as a
reuptake inhibitorA reuptake inhibitor , also known as a transporter blocker, is a drug which inhibits the plasmalemmal transporter-mediated reuptake of a neurotransmitter from the synapse into the pre-synaptic neuron, leading to an increase in the extracellular concentrations of the neurotransmitter and therefore...
for 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...
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...
by blocking the
actionThe action of drugs on the human body is called pharmacodynamics, and what the body does with the drug is called pharmacokinetics. The drugs that enter the human tend to stimulate certain receptors, ion channels, act on enzymes or transporter proteins...
of the
dopamine transporterThe dopamine transporter is a membrane-spanning protein that binds the neurotransmitter dopamine; DAT provides the primary mechanism through which dopamine is cleared from synapses, transporting dopamine from the synapse into a neuron...
(DAT). This in turn leads to increased
extracellularIn cell biology, molecular biology and related fields, the word extracellular means "outside the cell". This space is usually taken to be outside the plasma membranes, and occupied by fluid...
concentrationIn chemistry, concentration is the measure of how much of a given substance there is mixed with another substance. This can apply to any sort of chemical mixture, but most frequently the concept is limited to homogeneous solutions, where it refers to the amount of solute in the solvent.To...
s of dopamine and therefore an increase in
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...
neurotransmissionNeurotransmission , also called synaptic transmission, is an electrical movement within synapses caused by a propagation of nerve impulses...
.
DRIs may be used in the clinical treatment of
attention-deficit hyperactivity disorderAttention-deficit hyperactivity disorder is a neurobehavioral developmental disorder. ADHD is primarily characterized by "the co-existence of attentional problems and hyperactivity, with each behavior occurring infrequently alone." While symptoms may appear to be innocent and merely annoying...
(ADHD),
narcolepsyNarcolepsy is chronic sleep disorder, or dyssomnia. The condition is characterized by excessive daytime sleepiness in which a person experiences extreme fatigue and possibly falls asleep at inappropriate times, such as while at work or at school...
, and
fatigueFatigue may refer to:*Fatigue - medical aspects of tiredness in humans**Chronic fatigue syndrome - an illness of the central nervous system*Fatigue - failure by repeated stress in materials...
or lethargy as
stimulantStimulants, also sometimes called psychostimulants, are psychoactive drugs which induce temporary improvements in either mental or physical function or both. Examples of these kinds of effects may include enhanced alertness, wakefulness, and locomotion, among others...
s,
obesityObesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...
as
anorecticAn anorectic or anorexic , also known as anorexigenic or appetite suppressant, is a dietary supplements and/or drug which reduces appetite, food consumption, and as a result, causes weight loss to occur.-List of Anorectics:Numerous pharmaceutical compounds are marketed as appetite suppressants.The...
s or appetite suppressants for
weight lossWeight loss, in the context of medicine, health or physical fitness, is a reduction of the total body mass, due to a mean loss of fluid, body fat or adipose tissue and/or lean mass, namely bone mineral deposits, muscle, tendon and other connective tissue...
purposes, as well as
mood disorderA mood disorder is the term given for a group of diagnoses in the Diagnostic and Statistical Manual of Mental Disorders classification system where a disturbance in the person's mood is hypothesized to be the main underlying feature...
s such as major depressive disorder (MDD) usually of the treatment-resistant or
atypicalAtypical depression is a subtype of dysthymia and major depression characterized by mood reactivity — being able to experience improved mood in response to positive events. In contrast, sufferers of "melancholic" depression generally cannot experience positive moods, even when good things happen...
variants as
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,
social phobiaSocial phobia may refer to any of the following conditions:* Social anxiety - the experience of anxiety regarding social situations, interactions with others or being evaluated or scrutinized by other people* Social anxiety disorder - a diagnosis within the mental health professions referring to...
(SP) or
social anxiety disorderSocial anxiety disorder , also known as social anxiety or social phobia is a diagnosis within psychiatry and other mental health professions referring to excessive social anxiety causing considerable distress and impaired ability to function in at least some areas of daily life...
(SAD) and perhaps other
anxiety disorderAnxiety disorder is a blanket term covering several different forms of abnormal and pathological fears and anxieties which only came under the aegis of psychiatry at the very end of the 19th century. Current psychiatric diagnostic criteria recognize a wide variety of anxiety disorders...
s as
anxiolyticAn anxiolytic is a drug used for the treatment of symptoms of anxiety. Anxiolytics have been shown to be useful in the treatment of anxiety disorders, as have antidepressants such as the selective serotonin reuptake inhibitors .Though not anxiolytics, beta-receptor blockers such as propranolol and...
s,
parkinsonismParkinsonism is a neurological syndrome characterized by tremor, hypokinesia, rigidity, and postural instability. The underlying causes of parkinsonism are numerous, and diagnosis can be complex...
such as that seen in
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....
as antiparkinsonian agents,
drug addictionDrug addiction is a pathological condition which arises due to frequent drug use. The disorder of addiction involves the progression of acute drug use to the development of drug-seeking behavior, the vulnerability to relapse, and the decreased, slowed ability to respond to naturally rewarding stimuli...
and/or
dependencePhysical dependence refers to a state resulting from chronic use of a drug that has produced tolerance and where negative physical symptoms of withdrawal result from abrupt discontinuation or dosage reduction. Physical dependence can develop from low-dose therapeutic use of certain medications as...
as anticraving agents, and both as
augmentationAugmentation is the combination of two or more drugs to achieve better treatment results....
s and to offset some of the side effects of other drugs like 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...
s (SSRIs) such as
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:...
.
DRIs can induce a wide range of psychological and physiological effects, including the following:
It should be noted, however, that many of these properties are dependent on whether the DRI in question is capable of crossing the blood-brain-barrier (BBB).
A
dopamine reuptake inhibitor (
DRI,
DARI) is a type of
drugA drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...
which acts as a
reuptake inhibitorA reuptake inhibitor , also known as a transporter blocker, is a drug which inhibits the plasmalemmal transporter-mediated reuptake of a neurotransmitter from the synapse into the pre-synaptic neuron, leading to an increase in the extracellular concentrations of the neurotransmitter and therefore...
for 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...
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...
by blocking the
actionThe action of drugs on the human body is called pharmacodynamics, and what the body does with the drug is called pharmacokinetics. The drugs that enter the human tend to stimulate certain receptors, ion channels, act on enzymes or transporter proteins...
of the
dopamine transporterThe dopamine transporter is a membrane-spanning protein that binds the neurotransmitter dopamine; DAT provides the primary mechanism through which dopamine is cleared from synapses, transporting dopamine from the synapse into a neuron...
(DAT). This in turn leads to increased
extracellularIn cell biology, molecular biology and related fields, the word extracellular means "outside the cell". This space is usually taken to be outside the plasma membranes, and occupied by fluid...
concentrationIn chemistry, concentration is the measure of how much of a given substance there is mixed with another substance. This can apply to any sort of chemical mixture, but most frequently the concept is limited to homogeneous solutions, where it refers to the amount of solute in the solvent.To...
s of dopamine and therefore an increase in
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...
neurotransmissionNeurotransmission , also called synaptic transmission, is an electrical movement within synapses caused by a propagation of nerve impulses...
.
Indications
DRIs may be used in the clinical treatment of
attention-deficit hyperactivity disorderAttention-deficit hyperactivity disorder is a neurobehavioral developmental disorder. ADHD is primarily characterized by "the co-existence of attentional problems and hyperactivity, with each behavior occurring infrequently alone." While symptoms may appear to be innocent and merely annoying...
(ADHD),
narcolepsyNarcolepsy is chronic sleep disorder, or dyssomnia. The condition is characterized by excessive daytime sleepiness in which a person experiences extreme fatigue and possibly falls asleep at inappropriate times, such as while at work or at school...
, and
fatigueFatigue may refer to:*Fatigue - medical aspects of tiredness in humans**Chronic fatigue syndrome - an illness of the central nervous system*Fatigue - failure by repeated stress in materials...
or lethargy as
stimulantStimulants, also sometimes called psychostimulants, are psychoactive drugs which induce temporary improvements in either mental or physical function or both. Examples of these kinds of effects may include enhanced alertness, wakefulness, and locomotion, among others...
s,
obesityObesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...
as
anorecticAn anorectic or anorexic , also known as anorexigenic or appetite suppressant, is a dietary supplements and/or drug which reduces appetite, food consumption, and as a result, causes weight loss to occur.-List of Anorectics:Numerous pharmaceutical compounds are marketed as appetite suppressants.The...
s or appetite suppressants for
weight lossWeight loss, in the context of medicine, health or physical fitness, is a reduction of the total body mass, due to a mean loss of fluid, body fat or adipose tissue and/or lean mass, namely bone mineral deposits, muscle, tendon and other connective tissue...
purposes, as well as
mood disorderA mood disorder is the term given for a group of diagnoses in the Diagnostic and Statistical Manual of Mental Disorders classification system where a disturbance in the person's mood is hypothesized to be the main underlying feature...
s such as major depressive disorder (MDD) usually of the treatment-resistant or
atypicalAtypical depression is a subtype of dysthymia and major depression characterized by mood reactivity — being able to experience improved mood in response to positive events. In contrast, sufferers of "melancholic" depression generally cannot experience positive moods, even when good things happen...
variants as
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,
social phobiaSocial phobia may refer to any of the following conditions:* Social anxiety - the experience of anxiety regarding social situations, interactions with others or being evaluated or scrutinized by other people* Social anxiety disorder - a diagnosis within the mental health professions referring to...
(SP) or
social anxiety disorderSocial anxiety disorder , also known as social anxiety or social phobia is a diagnosis within psychiatry and other mental health professions referring to excessive social anxiety causing considerable distress and impaired ability to function in at least some areas of daily life...
(SAD) and perhaps other
anxiety disorderAnxiety disorder is a blanket term covering several different forms of abnormal and pathological fears and anxieties which only came under the aegis of psychiatry at the very end of the 19th century. Current psychiatric diagnostic criteria recognize a wide variety of anxiety disorders...
s as
anxiolyticAn anxiolytic is a drug used for the treatment of symptoms of anxiety. Anxiolytics have been shown to be useful in the treatment of anxiety disorders, as have antidepressants such as the selective serotonin reuptake inhibitors .Though not anxiolytics, beta-receptor blockers such as propranolol and...
s,
parkinsonismParkinsonism is a neurological syndrome characterized by tremor, hypokinesia, rigidity, and postural instability. The underlying causes of parkinsonism are numerous, and diagnosis can be complex...
such as that seen in
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....
as antiparkinsonian agents,
drug addictionDrug addiction is a pathological condition which arises due to frequent drug use. The disorder of addiction involves the progression of acute drug use to the development of drug-seeking behavior, the vulnerability to relapse, and the decreased, slowed ability to respond to naturally rewarding stimuli...
and/or
dependencePhysical dependence refers to a state resulting from chronic use of a drug that has produced tolerance and where negative physical symptoms of withdrawal result from abrupt discontinuation or dosage reduction. Physical dependence can develop from low-dose therapeutic use of certain medications as...
as anticraving agents, and both as
augmentationAugmentation is the combination of two or more drugs to achieve better treatment results....
s and to offset some of the side effects of other drugs like 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...
s (SSRIs) such as
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:...
.
General
DRIs can induce a wide range of psychological and physiological effects, including the following:
It should be noted, however, that many of these properties are dependent on whether the DRI in question is capable of crossing the blood-brain-barrier (BBB). Those that do not will only produce
peripheralA peripheral is a device attached to a host computer but not part of it whose primary functionality is dependent upon the host, and can therefore be considered as expanding the host's capabilities, while not forming part of the system's core architecture....
effects.
Overdose
At very high doses and/or with chronic administration characterized by overdose, stimulant psychosis may develop, the
symptomA symptom is a departure from normal function or feeling which is noticed by a patient, indicating the presence of disease or abnormality...
s of which can include the following:
Additionally, potential
incarcerationIncarceration is the detention of a person in gaol or prison. People are most commonly incarcerated upon suspicion or conviction of committing a crime. Incarceration rates, when measured by the United Nations, are considered distinct and separate from the imprisonment of political prisoners and...
, hospitalization,
institutionalizationA psychiatric hospital, sometimes known as an asylum, is a hospital specializing in the treatment of serious mental illness, usually for relatively long-term inpatients....
, and/or
deathDeath is the termination of the biological functions that define a living organism. It refers to both a particular event and to the condition that results thereby. The true nature of the latter has for millennia been a central concern of the world's religious traditions and of philosophical...
, on account of extreme
erraticRecklessness is disregard for or indifference to the dangers of a situation or for the consequences of one's actions....
behaviorBehavior or behaviour refers to the actions or reactions of an object or organism, usually in relation to the environment. Behavior can be conscious or subconscious, overt or covert, and voluntary or involuntary....
which may include acts of
crimeCrime is the breach of one or more rules or laws for which some governing authority, via mechanisms such as police power, may ultimately prescribe a conviction...
,
assaultAssault is a crime of violence against another person. In some jurisdictions, including Australia and New Zealand, assault refers to an act that causes another to apprehend immediate and personal violence, while in other jurisdictions, such as the United States, assault may refer only to the threat...
, accidental or intentional self-injury, and/or
suicideSuicide is the intentional killing of one's self. Many dictionaries also note the metaphorical sense of "willful destruction of one's self-interest"...
, as well as
illicitThe prohibition of drugs through sumptuary legislation or religious law is a common means of attempting to control drug use. Prohibition of drugs has existed at various levels of government or other authority, from the Middle Ages to the present....
drug abuseDrug abuse has a huge range of definitions related to taking a psychoactive drug or performance enhancing drug for a non-therapeutic or non-medical effect. All of these definitions imply a negative judgement of the drug use in question...
, may ensue under such circumstances.
Abuse
Due to their strong
rewardingIn neuroscience, the reward system is a collection of brain structures which attempts to regulate and control behavior by inducing pleasurable effects.-Psychological reward:...
and
reinforcingIn operant conditioning, reinforcement occurs when an event following a response causes an increase in the probability of that response occurring in the future...
properties, DRIs are notorious for their high
abuse potentialDrug abuse has a huge range of definitions related to taking a psychoactive drug or performance enhancing drug for a non-therapeutic or non-medical effect. All of these definitions imply a negative judgement of the drug use in question...
and liability to cause
cravingWhen going through withdrawal, craving is a psychological urge to administer a discontinued medication, recreational drug and/or alcohol.-Duration:The duration that cravings last after discontinuation varies substantially between different addictive drugs...
s,
addictionDrug addiction is a pathological condition which arises due to frequent drug use. The disorder of addiction involves the progression of acute drug use to the development of drug-seeking behavior, the vulnerability to relapse, and the decreased, slowed ability to respond to naturally rewarding stimuli...
, and
dependencePhysical dependence refers to a state resulting from chronic use of a drug that has produced tolerance and where negative physical symptoms of withdrawal result from abrupt discontinuation or dosage reduction. Physical dependence can develop from low-dose therapeutic use of certain medications as...
. Pure DRIs such as
cocaineCocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system and an appetite suppressant...
and combination
releasing agentA releasing agent , or simply releaser, is a drug which induces the release of a neurotransmitter from the pre-synaptic neuron into the synapse, leading to an increase in the extracellular concentrations of the neurotransmitter...
s such as
amphetamineAmphetamine is a psychostimulant drug that is known to produce increased wakefulness and focus in association with decreased fatigue and appetite. Amphetamine is related to drugs such as methamphetamine and dextroamphetamine, which are a group of potent drugs that act by increasing levels of...
(Adderall, Dexedrine),
methamphetamineMethamphetamine also known as metamfetamine , dextromethamphetamine, methylamphetamine, N-methylamphetamine, and desoxyephedrine) is a psychostimulant and sympathomimetic drug. Methamphetamine enters the brain and triggers a cascading release of dopamine, serotonin and norepinephrine...
(Desoxyn),
MDMAMDMA is a psychoactive amphetamine drug with entactogenic, psychedelic, and stimulant effects....
("Ecstasy"), and 4-methylaminorex are widely
abusedRecreational drug use is the use of psychoactive drugs for recreational purposes rather than for work, approved medical or spiritual purposes, although the distinction is not always clear ....
throughout the
worldWorld is a highly common name for the planet Earth, but it was originally used to mean the sum of human civilization living on it, specifically human experience, history, or the 'human condition' in general....
. It is estimated that there are approximately six million people addicted to cocaine in the
United StatesThe United States of America is a federal constitutional republic comprising fifty states and a federal district...
(U.S.) alone.
Notably, some DRIs have a lower abuse potential than others. Those that have a slow
onsetIn pharmacology , absorption is the movement of a drug into the bloodstream.Absorption involves several phases...
and long
durationThe biological half-life or elimination half life of a substance is the time it takes for a substance to lose half of its pharmacologic, physiologic, or radiologic activity, as per the MeSH definition...
of
actionThe action of drugs on the human body is called pharmacodynamics, and what the body does with the drug is called pharmacokinetics. The drugs that enter the human tend to stimulate certain receptors, ion channels, act on enzymes or transporter proteins...
such as
bupropionBupropion is an atypical antidepressant that acts as a norepinephrine and dopamine reuptake inhibitor, and nicotinic antagonist...
(Wellbutrin, Zyban) and
methylphenidateMethylphenidate is the most commonly prescribed psychostimulant and is indicated in the treatment of attention-deficit hyperactivity disorder, Postural Orthostatic Tachycardia Syndrome and narcolepsy, although off-label uses include treating lethargy, depression, neural insult, and obesity.In...
(Ritalin, Focalin, Concerta) are typically much less reinforcing than faster acting ones which produce a rush like cocaine. In fact, bupropion is often used as a
maintenance therapyMaintenance therapy is a medical therapy that is designed to help a primary treatment succeed. For example, maintenance chemotherapy may be given to people who have a cancer in remission in an attempt to prevent a relapse...
for treating
stimulantStimulants, also sometimes called psychostimulants, are psychoactive drugs which induce temporary improvements in either mental or physical function or both. Examples of these kinds of effects may include enhanced alertness, wakefulness, and locomotion, among others...
addictionThe term "addiction" is used in many contexts to describe an obsession, compulsion, or excessive psychological dependence, such as: drug addiction The term "addiction" is used in many contexts to describe an obsession, compulsion, or excessive psychological dependence, such as: drug addiction The...
. However, depending on the
route of administrationA route of administration in pharmacology and toxicology is the path by which a drug, fluid, poison, or other substance is brought into contact with the body....
(e.g.,
insufflationIn religious and magical practice, insufflation and exsufflation are ritual acts of blowing, breathing, hissing, or puffing that signify variously expulsion or renunciation of evil or of the devil , or infilling or blessing with good .In historical Christian practice, such blowing appears most...
,
inhalationInhalation is the movement of air from the external environment, through the air ways, and into the alveoli.Inhalation begins with the onset of contraction of the diaphragm, which results in expansion of the intrapleural space and an increase in negative pressure according to Boyle's Law...
, or
injectionInjection may refer to:* Injection , a method of putting liquid into the body with a syringe and a hollow needle that punctures the skin.* Injective function in mathematics, a function which associates distinct arguments to distinct values...
), the
pleasurablePleasure describes the broad class of mental states that humans and other animals experience as positive, enjoyable, or otherwise to be sought out. It thus includes more specific mental states such as happiness, entertainment, enjoyment, ecstasy, and euphoria...
effects of the DRI in question can be dramatically enhanced, potentially rendering those with only mild rewarding effects to become far more reinforcing than they would be under normal circumstances.
List of DRIs
Of the above listed agents, altropane, amfonelic acid, benocyclidine, DBL-583, difluoropine, GBR-12,935, ioflupane, and vanoxerine are all highly selective, pure DRIs, with no known, significant affinity for the serotonin or norepinephrine transporters or any other sites.
Dopamine releasing agents (DRAs) such as
amphetamineAmphetamine is a psychostimulant drug that is known to produce increased wakefulness and focus in association with decreased fatigue and appetite. Amphetamine is related to drugs such as methamphetamine and dextroamphetamine, which are a group of potent drugs that act by increasing levels of...
and
methamphetamineMethamphetamine also known as metamfetamine , dextromethamphetamine, methylamphetamine, N-methylamphetamine, and desoxyephedrine) is a psychostimulant and sympathomimetic drug. Methamphetamine enters the brain and triggers a cascading release of dopamine, serotonin and norepinephrine...
also function as DRIs secondary to their releasing action. To distinguish between DRIs and DRAs, the latter are not included in the above list. For a list of DRAs, see the
releasing agentA releasing agent , or simply releaser, is a drug which induces the release of a neurotransmitter from the pre-synaptic neuron into the synapse, leading to an increase in the extracellular concentrations of the neurotransmitter...
article. In correspondence with the previous paragraph, notably, to date, there are no known selective DRAs, as dissociating affinity between the dopamine and norepinephrine transporters has so far proven to be virtually impossible to achieve, likely on account of the very similar structure of the respective proteins.