Clonidine, sold under the brand name Catapres among others, is an α₂-adrenergic agonist medication used to treat high blood pressure, ADHD,

drug withdrawal Drug withdrawal, drug withdrawal syndrome, or substance withdrawal syndrome, is the group of symptoms that occur upon the abrupt discontinuation or decrease in the intake of pharmaceutical or recreational drugs. In order for the symptoms of wit ...

( alcohol, opioids, or

nicotine Nicotine is a natural product, naturally produced alkaloid in the nightshade family of plants (most predominantly in tobacco and ''Duboisia hopwoodii'') and is widely used recreational drug use, recreationally as a stimulant and anxiolytic. As ...

), menopausal flushing,

diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin w ...

spasticity Spasticity () is a feature of altered skeletal muscle performance with a combination of paralysis, increased tendon reflex activity, and hypertonia. It is also colloquially referred to as an unusual "tightness", stiffness, or "pull" of muscles ...

, and certain pain conditions. It is used by mouth, by injection, or as a skin patch. Onset of action is typically within an hour with the effects on blood pressure lasting for up to eight hours. Common side effect include dry mouth, dizziness, headaches, hypotension, and sleepiness. Severe side effects may include hallucinations, heart arrhythmias, and confusion. If rapidly stopped, withdrawal effects may occur. Use during

pregnancy Pregnancy is the time during which one or more offspring develops (gestation, gestates) inside a woman, woman's uterus (womb). A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occur ...

breastfeeding Breastfeeding, or nursing, is the process by which human breast milk is fed to a child. Breast milk may be from the breast, or may be expressed by hand or pumped and fed to the infant. The World Health Organization (WHO) recommends that br ...

is not recommended. Clonidine lowers blood pressure by stimulating α₂ receptors in the brain, which results in relaxation of many arteries. Clonidine was patented in 1961 and came into medical use in 1966. It is available as a generic medication. In 2020, it was the 75th most commonly prescribed medication in the United States, with more than 9million prescriptions.

Medical uses

Clonidine is used to treat high blood pressure,

attention deficit hyperactivity disorder Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by excessive amounts of inattention, hyperactivity, and impulsivity that are pervasive, impairing in multiple contexts, and otherwise age-inap ...

(ADHD),

( alcohol, opioids, or smoking), menopausal flushing,

, and certain pain conditions. It also sees some use off-label for episodic

insomnia Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...

, restless-legs syndrome, and

anxiety Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...

, among other uses.

Resistant hypertension

Clonidine may be effective for lowering blood pressure in people with resistant hypertension. Clonidine works by slowing the pulse rate and exerts a reduction of serum concentrations of

renin Renin (etymology and pronunciation), also known as an angiotensinogenase, is an aspartic protease protein and enzyme secreted by the kidneys that participates in the body's renin–angiotensin–aldosterone system (RAAS)—also known as the r ...

, aldosterone, and catecholamines.

Attention deficit hyperactivity disorder

Clonidine may improve symptoms of attention deficit hyperactivity disorder in some people but causes many adverse effects and the beneficial effect is modest. In Australia, clonidine is an accepted but not approved use for ADHD by the TGA. Clonidine, along with

methylphenidate Methylphenidate, sold under the brand names Ritalin and Concerta among others, is the most widely prescribed central nervous system (CNS) stimulant medication used to treat attention deficit hyperactivity disorder (ADHD) and, to a lesser exten ...

, has been studied for treatment of ADHD. While not as effective as methylphenidate in treating ADHD, clonidine does offer some benefit; it can also be useful in combination with stimulant medications. Some studies show clonidine to be more sedating than

guanfacine Guanfacine, sold under the brand name Tenex among others, is an oral medication used to treat attention deficit hyperactivity disorder (ADHD) and high blood pressure. Guanfacine is FDA-approved for monotherapy treatment of ADHD as well as being ...

, which may be better at bedtime along with an arousing stimulant in the morning. Clonidine has been used to reduce sleep disturbances in ADHD, including to help offset stimulant-associated

Drug withdrawal

Clonidine may be used to ease drug withdrawal symptoms associated with abruptly stopping the long-term use of opioids, alcohol, benzodiazepines and

. It can alleviate

opioid withdrawal Opioid withdrawal is a set of symptoms (a syndrome) arising from the sudden withdrawal or reduction of opioids where previous usage has been heavy and prolonged. Signs and symptoms of withdrawal can include drug craving, anxiety, restless legs, ...

symptoms by reducing the sympathetic nervous system response such as

tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ( ...

and hypertension,

hyperhidrosis Hyperhidrosis is a condition characterized by abnormally increased sweating, in excess of that required for regulation of body temperature. Although primarily a benign physical burden, hyperhidrosis can deteriorate quality of life from a psycholog ...

(excessive sweating), hot and cold flashes, and

akathisia Akathisia is a movement disorder characterized by a subjective feeling of inner restlessness accompanied by mental distress and an inability to sit still. Usually, the legs are most prominently affected. Those affected may fidget, rock back a ...

. It may also be helpful in aiding smokers to quit. The sedation effect can also be useful. Clonidine may also reduce severity of

neonatal abstinence syndrome Neonatal withdrawal or neonatal abstinence syndrome (NAS) or neonatal opioid withdrawal syndrome (NOWS) is a withdrawal syndrome of infants after birth caused by ''in utero'' exposure to drugs of dependence, most commonly opioids. Common signs and ...

in infants born to mothers that are using certain drugs, particularly opioids. In infants with neonatal withdrawal syndrome, clonidine may improve the neonatal intensive care unit Network Neurobehavioral Score. Clonidine has also been suggested as a treatment for rare instances of

dexmedetomidine Dexmedetomidine, sold under the trade name Precedex among others, is a drug used in humans for sedation. Veterinarians use dexmedetomidine for similar purposes in treating cats, dogs, and horses. It is also used in humans to treat acute agitation ...

withdrawal.

Spasticity

Clonidine has some role in the treatment of spasticity, acting principally by inhibiting excessive sensory transmission below the level of injury. Its use, however, is mainly as a second or third line agent, due to side effects such as

hypotension Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dia ...

, bradycardia, and

drowsiness Somnolence (alternatively sleepiness or drowsiness) is a state of strong desire for sleep, or sleeping for unusually long periods (compare hypersomnia). It has distinct meanings and causes. It can refer to the usual state preceding falling asleep ...

Other uses

Clonidine also has several

off-label use Off-label use is the use of pharmaceutical drugs for an unapproved indication or in an unapproved age group, dosage, or route of administration. Both prescription drugs and over-the-counter drugs (OTCs) can be used in off-label ways, although ...

s, and has been prescribed to treat

psychiatric disorder A mental disorder, also referred to as a mental illness or psychiatric disorder, is a behavioral or mental pattern that causes significant distress or impairment of personal functioning. Such features may be persistent, relapsing and remitt ...

s including

stress Stress may refer to: Science and medicine * Stress (biology), an organism's response to a stressor such as an environmental condition * Stress (linguistics), relative emphasis or prominence given to a syllable in a word, or to a word in a phrase ...

sleep disorders A sleep disorder, or somnipathy, is a medical disorder of an individual's sleep patterns. Some sleep disorders are severe enough to interfere with normal physical, mental, social and emotional functioning. Polysomnography and actigraphy are tests ...

hyperarousal The fight-or-flight or the fight-flight-or-freeze response (also called hyperarousal or the acute stress response) is a physiological reaction that occurs in response to a perceived harmful event, attack, or threat to survival. It was first des ...

caused by

post-traumatic stress disorder Post-traumatic stress disorder (PTSD) is a mental and behavioral disorder that can develop because of exposure to a traumatic event, such as sexual assault, warfare, traffic collisions, child abuse, domestic violence, or other threats on ...

borderline personality disorder Borderline personality disorder (BPD), also known as emotionally unstable personality disorder (EUPD), is a personality disorder characterized by a long-term pattern of unstable interpersonal relationships, distorted sense of self, and strong ...

, and other anxiety disorders. Clonidine is also a mild

sedative A sedative or tranquilliser is a substance that induces sedation by reducing irritability or excitement. They are CNS depressants and interact with brain activity causing its deceleration. Various kinds of sedatives can be distinguished, but t ...

, and can be used as

premedication Premedication is using medication before some other therapy (usually surgery or chemotherapy) to prepare for that forthcoming therapy. Typical examples include premedicating with a sedative or analgesic before surgery; using prophylactic (prevent ...

before surgery or procedures. It has also been studied as a way to calm acute manic episodes. Its epidural use for pain during heart attack, and postoperative and intractable pain has also been studied extensively. Clonidine can be used in

restless legs syndrome Restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED), is generally a long-term disorder that causes a strong urge to move one's legs. There is often an unpleasant feeling in the legs that improves somewhat by moving them. This ...

. It can also be used to treat facial flushing and redness associated with

rosacea Rosacea is a long-term skin condition that typically affects the face. It results in redness, pimples, swelling, and small and superficial dilated blood vessels. Often, the nose, cheeks, forehead, and chin are most involved. A red, enlarg ...

. It has also been successfully used topically in a clinical trial as a treatment for diabetic neuropathy. Clonidine can also be used for

migraine Migraine (, ) is a common neurological disorder characterized by recurrent headaches. Typically, the associated headache affects one side of the head, is pulsating in nature, may be moderate to severe in intensity, and could last from a few hou ...

headaches and

hot flash Hot flashes (also known as hot flushes) are a form of flushing, often caused by the changing hormone levels that are characteristic of menopause. They are typically experienced as a feeling of intense heat with sweating and rapid heartbeat, and ...

es associated with

menopause Menopause, also known as the climacteric, is the time in women's lives when menstrual periods stop permanently, and they are no longer able to bear children. Menopause usually occurs between the age of 47 and 54. Medical professionals often ...

. Clonidine has also been used to treat refractory

associated with

irritable bowel syndrome Irritable bowel syndrome (IBS) is a "disorder of gut-brain interaction" characterized by a group of symptoms that commonly include abdominal pain and or abdominal bloating and changes in the consistency of bowel movements. These symptoms may ...

fecal incontinence Fecal incontinence (FI), or in some forms encopresis, is a lack of control over defecation, leading to involuntary loss of bowel contents, both liquid stool elements and mucus, or solid feces. When this loss includes flatus (gas), it is referre ...

, diabetes, diarrhea associated with opioid withdrawal, intestinal failure, neuroendocrine tumors, and

cholera Cholera is an infection of the small intestine by some strains of the bacterium ''Vibrio cholerae''. Symptoms may range from none, to mild, to severe. The classic symptom is large amounts of watery diarrhea that lasts a few days. Vomiting and ...

. Clonidine can be used in the treatment of

Tourette syndrome Tourette syndrome or Tourette's syndrome (abbreviated as TS or Tourette's) is a common neurodevelopmental disorder that begins in childhood or adolescence. It is characterized by multiple movement (motor) tics and at least one vocal (phonic) ...

(specifically for

tics A tic is a sudden, repetitive, nonrhythmic motor movement or vocalization involving discrete muscle groups.American Psychiatric Association (2000)DSM-IV-TR: Tourette's Disorder.''Diagnostic and Statistical Manual of Mental Disorders'', 4th ed., ...

). Clonidine has also had some success in clinical trials for helping to remove or ameliorate the symptoms of hallucinogen persisting perception disorder (HPPD). Injection of α₂ receptor agonists into the knee joint space, including clonidine, may reduce the severity of knee pain after

arthroscopic Arthroscopy (also called arthroscopic or keyhole surgery) is a minimally invasive surgical procedure on a joint in which an examination and sometimes treatment of damage is performed using an arthroscope, an endoscope that is inserted into the jo ...

knee surgery. Light-activated derivatives of clonidine (adrenoswitches) have been developed for research purposes and shown to control pupillary reflex with light in blind mice by topical application.

Clonidine suppression test

The reduction in circulating norepinephrine by clonidine was used in the past as an investigatory test for

phaeochromocytoma Pheochromocytoma (PHEO or PCC) is a rare tumor of the adrenal medulla composed of chromaffin cells, also known as pheochromocytes. When a tumor composed of the same cells as a pheochromocytoma develops outside the adrenal gland, it is referred t ...

, which is a catecholamine-synthesizing tumor, usually found in the adrenal medulla. In a clonidine suppression test, plasma catecholamine levels are measured before and 3 hours after a 0.3 mg oral test dose has been given to the patient. A positive test occurs if there is no decrease in plasma levels.

Pregnancy and breastfeeding

Clonidine is classed by the FDA as pregnancy category C. It is classified by the TGA of Australia as pregnancy category B3, which means that it has shown some detrimental effects on fetal development in animal studies, although the relevance of this to human beings is unknown. Clonidine appears in high concentration in breast milk and nursing infants have approximately 2/3 of serum clonidine concentrations as the mother. Caution is warranted in women who are pregnant, planning to become pregnant, or are breastfeeding.

Adverse effects

The principal adverse effects of clonidine are sedation, dry mouth, and hypotension (low blood pressure). By frequency Very common (>10% frequency): * Dizziness *

Orthostatic hypotension Orthostatic hypotension, also known as postural hypotension, is a medical condition wherein a person's blood pressure drops when standing up or sitting down. Primary orthostatic hypertension is also often referred to as neurogenic orthostatic hyp ...

Somnolence Somnolence (alternatively sleepiness or drowsiness) is a state of strong desire for sleep, or sleeping for unusually long periods (compare hypersomnia). It has distinct meanings and causes. It can refer to the usual state preceding falling asleep ...

(dose-dependent) *

Dry mouth Xerostomia, also known as dry mouth, is dryness in the mouth, which may be associated with a change in the composition of saliva, or reduced salivary flow, or have no identifiable cause. This symptom is very common and is often seen as a side eff ...

* Headache (dose-dependent) * Fatigue * Skin reactions (if given transdermally) *

Hypotension Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dia ...

Common (1-10% frequency): * Anxiety * Constipation * Sedation (dose-dependent) * Nausea/vomiting * Malaise * Abnormal LFTs * Rash * Weight gain/loss * Pain below the ear (from salivary gland) * Erectile dysfunction Uncommon (0.1-1% frequency): * Delusional perception * Hallucination * Nightmare *

Paresthesia Paresthesia is an abnormal sensation of the skin (tingling, pricking, chilling, burning, numbness) with no apparent physical cause. Paresthesia may be transient or chronic, and may have any of dozens of possible underlying causes. Paresthesias ar ...

Sinus bradycardia Sinus bradycardia is a sinus node dysfunction giving a heart rate that is lower than the normal 60–100 beats per minute (bpm) in humans. Bradycardia is generally defined to be a heart rate of under 60 bpm. Signs and symptoms The decreased hea ...

Raynaud's phenomenon Raynaud syndrome, also known as Raynaud's phenomenon, eponymously named after the physician Auguste Gabriel Maurice Raynaud, who first described it in his doctoral thesis in 1862, is a medical condition in which the spasm of small arteries cau ...

Pruritus Itch (also known as pruritus) is a sensation that causes the desire or reflex to scratch. Itch has resisted many attempts to be classified as any one type of sensory experience. Itch has many similarities to pain, and while both are unpleasant ...

Urticaria Hives, also known as urticaria, is a kind of skin rash with red, raised, itchy bumps. Hives may burn or sting. The patches of rash may appear on different body parts, with variable duration from minutes to days, and does not leave any long-last ...

Rare (<0.1% frequency): *

Gynaecomastia Gynecomastia (also spelled gynaecomastia) is the abnormal non-cancerous enlargement of one or both breasts in males due to the growth of breast tissue as a result of a hormone imbalance between estrogens and androgens. Updated by Brent Wisse (1 ...

* Impaired ability to cry *

Atrioventricular block Atrioventricular block (AV block) is a type of heart block that occurs when the electrical signal traveling from the atria, or the upper chambers of the heart, to ventricles, or the lower chambers of the heart, is impaired. Normally, the sinoatr ...

* Nasal dryness * Colonic pseudo-obstruction *

Alopecia Hair loss, also known as alopecia or baldness, refers to a loss of hair from part of the head or body. Typically at least the head is involved. The severity of hair loss can vary from a small area to the entire body. Inflammation or scar ...

* Hyperglycemia

Withdrawal

Because clonidine suppresses sympathetic outflow, resulting in lower blood pressure, sudden discontinuation can result in acute hypertension due to a rebound in sympathetic outflow. In extreme cases, this can result in a

hypertensive crisis Severely elevated blood pressure (equal to or greater than a systolic 180 or diastolic of 120—sometimes termed malignant or accelerated hypertension) is referred to as a hypertensive crisis, as blood pressure at this level confers a high risk ...

, which is a medical emergency. Clonidine therapy should generally be gradually tapered when discontinuing therapy to avoid

rebound effects The rebound effect, or rebound phenomenon, is the emergence or re-emergence of symptoms that were either absent or controlled while taking a medication, but appear when that same medication is discontinued, or reduced in dosage. In the case of re ...

from occurring. Treatment of clonidine withdrawal hypertension depends on the severity of the condition. Reintroduction of clonidine for mild cases,

alpha Alpha (uppercase , lowercase ; grc, ἄλφα, ''álpha'', or ell, άλφα, álfa) is the first letter of the Greek alphabet. In the system of Greek numerals, it has a value of one. Alpha is derived from the Phoenician letter aleph , whic ...

and

beta Beta (, ; uppercase , lowercase , or cursive ; grc, βῆτα, bē̂ta or ell, βήτα, víta) is the second letter of the Greek alphabet. In the system of Greek numerals, it has a value of 2. In Modern Greek, it represents the voiced labiod ...

blockers for more urgent situations. Beta blockers never should be used alone to treat clonidine withdrawal as alpha vasoconstriction would still continue.

Pharmacology

Mechanism of action

Clonidine crosses the blood–brain barrier.

High blood pressure

Clonidine treats high blood pressure by stimulating α₂ receptors in the brainstem, which decreases

peripheral vascular resistance Vascular resistance is the resistance that must be overcome to push blood through the circulatory system and create flow. The resistance offered by the systemic circulation is known as the systemic vascular resistance (SVR) or may sometimes be cal ...

, lowering blood pressure. It has specificity towards the

presynaptic In the nervous system, a synapse is a structure that permits a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron or to the target effector cell. Synapses are essential to the transmission of nervous impulses from ...

α₂ receptors in the

vasomotor center The vasomotor center (VMC) is a portion of the medulla oblongata. Together with the cardiovascular center and respiratory center, it regulates blood pressure. It also has a more minor role in other homeostatic processes. Upon increase in carbon ...

in the

brainstem The brainstem (or brain stem) is the posterior stalk-like part of the brain that connects the cerebrum with the spinal cord. In the human brain the brainstem is composed of the midbrain, the pons, and the medulla oblongata. The midbrain is cont ...

. This binding has a sympatholytic effect, suppresses release of

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad'', ...

, ATP, renin, and

neuropeptide Y Neuropeptide Y (NPY) is a 36 amino-acid neuropeptide that is involved in various physiological and homeostatic processes in both the central and peripheral nervous systems. NPY has been identified as the most abundant peptide present in the ma ...

which if released would increase

vascular resistance Vascular resistance is the resistance that must be overcome to push blood through the circulatory system and create flow. The resistance offered by the systemic circulation is known as the systemic vascular resistance (SVR) or may sometimes be cal ...

. Clonidine also acts as an agonist at imidazoline-1 (I₁) receptors in the brain, and it is hypothesized that this effect may contribute to reducing blood pressure by reducing signaling in the sympathetic nervous system; this effect acts upstream of the central α₂ agonist effect of clonidine. Clonidine may also cause bradycardia, theoretically by increasing signaling through the vagus nerve. When given intravenously, clonidine can temporarily increase blood pressure by stimulating α₁ receptors in smooth muscles in blood vessels. This hypertensive effect is not usual when clonidine is given by mouth or by the

transdermal Transdermal is a route of administration wherein active ingredients are delivered across the skin for systemic distribution. Examples include transdermal patches used for medicine delivery. The drug is administered in the form of a patch or ointme ...

route. Plasma concentration of clonidine exceeding 2.0 ng/mL does not provide further blood pressure reduction.

Attention deficit hyperactivity disorder

Structural_comparison_of_norepinephrine_and_clonidine

In the setting of

(ADHD), clonidine's molecular mechanism of action occurs due to its agonism at the

alpha-2A adrenergic receptor The alpha-2A adrenergic receptor (α2A adrenoceptor), also known as ADRA2A, is an α2 adrenergic receptor, and also denotes the human gene encoding it. Receptor α2 adrenergic receptors include 3 highly homologous subtypes: α2A, α2B, and α2 ...

, the subtype of the adrenergic receptor that is most principally found in the brain. Within the brain, the alpha-2A adrenergic receptors are found within the

prefrontal cortex In mammalian brain anatomy, the prefrontal cortex (PFC) covers the front part of the frontal lobe of the cerebral cortex. The PFC contains the Brodmann areas BA8, BA9, BA10, BA11, BA12, BA13, BA14, BA24, BA25, BA32, BA44, BA45, BA46 ...

(PFC), among other areas. The alpha-2A adrenergic receptors are found on the presynaptic cleft of a given neuron, and, when activated by an agonist, the effect on downstream neurons is inhibitory. The inhibition is accomplished by preventing the secretion of the neurotransmitter

. Thus, clonidine's agonism on alpha-2A adrenergic receptors in the PFC inhibits the action of downstream neurons by preventing the secretion of norepinephrine. This mechanism is similar to the brain's physiological inhibition of PFC neurons by the

locus ceruleus The locus coeruleus () (LC), also spelled locus caeruleus or locus ceruleus, is a nucleus in the pons of the brainstem involved with physiological responses to stress and panic. It is a part of the reticular activating system. The locus coeru ...

(LC), which secretes norepinephrine into the PFC. Although norepinephrine can also bind to target adrenergic receptors on the downstream neuron (otherwise inducing a stimulatory effect), norepinephrine also binds to alpha-2A adrenergic receptors (akin to clonidine's mechanism of action), inhibiting the release of norepinephrine by that neuron and inducing an inhibitory effect. Because the PFC is required for working memory and attention, it is thought that clonidine's inhibition of PFC neurons helps to eliminate irrelevant attention (and subsequent behaviors), improving the person's focus and correcting deficits in attention.

Growth hormone test

Clonidine stimulates release of HGH hormone from the hypothalamus, which in turn stimulates pituitary release of

growth hormone Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in h ...

. This effect has been used as part of a "growth hormone test," which can assist with diagnosing

growth hormone deficiency Growth hormone deficiency (GHD), or human growth hormone deficiency, is a medical condition resulting from not enough growth hormone (GH). Generally the most noticeable symptom is that an individual attains a short height. Newborns may also prese ...

in children.

Pharmacokinetics

After being ingested, clonidine is absorbed into the blood stream rapidly with an overall bioavailability around 70 - 80%. Peak concentrations in human plasma occur within 60–90 minutes for the "Immediate Release" (IR) version of the drug, which is shorter than the "Extended Release" (ER/XR) version. Clonidine is fairly lipid soluble with the logarithm of its partition coefficient (log P) equal to 1.6; to compare, the optimal log P to allow a drug that is active in the human

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...

to penetrate the

blood brain barrier Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the c ...

is 2.0. Less than half of the absorbed portion of an orally administered dose will be metabolized by the

liver The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...

into inactive

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

s, with roughly the other half being excreted unchanged by the

kidneys The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; bloo ...

. About one-fifth of an oral dose will not be absorbed, and is thus excreted in the feces. Work with liver microsomes shows in the liver clonidine is primarily metabolized by

CYP2D6 Cytochrome P450 2D6 (CYP2D6) is an enzyme that in humans is encoded by the ''CYP2D6'' gene. ''CYP2D6'' is primarily expressed in the liver. It is also highly expressed in areas of the central nervous system, including the substantia nigra. CYP2D ...

(66%),

CYP1A2 Cytochrome P450 1A2 (abbreviated CYP1A2), a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the human body. In humans, the CYP1A2 enzyme is encoded by the ''CYP1A2'' gene. Function ...

(10-20%), and

CYP3A Cytochrome P450, family 3, subfamily A, also known as CYP3A, is a human gene locus. A homologous locus is found in mice. The CYP3A locus includes all the known members of the 3A subfamily of the cytochrome P450 superfamily of genes. These genes ...

(0-20%) with negligible contributions from the less abundant enzymes

CYP3A5 Cytochrome P450 3A5 is a protein that in humans is encoded by the ''CYP3A5'' gene. Tissue distribution ''CYP3A5'' encodes a member of the cytochrome P450 superfamily of enzymes. Like most of the cytochrome P450, the CYP3A5 is expressed in the ...

CYP1A1 Cytochrome P450, family 1, subfamily A, polypeptide 1 is a protein that in humans is encoded by the ''CYP1A1'' gene. The protein is a member of the cytochrome P450 superfamily of enzymes. Function Metabolism of xenobiotics and drugs CYP1A1 ...

, and

CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine. It oxidizes small foreign organic molecules (xenobiotics), such as toxins or drugs, so that they can be removed from t ...

. 4-hydroxyclonidine, the main metabolite of clonidine, is also an alpha-2A agonist but is non lipophilic and is not believed to contribute to the effects of clonidine since it does not cross the blood–brain barrier. Measurements of the

half-life Half-life (symbol ) is the time required for a quantity (of substance) to reduce to half of its initial value. The term is commonly used in nuclear physics to describe how quickly unstable atoms undergo radioactive decay or how long stable at ...

of clonidine vary widely, between 6 and 23 hours, with the half-life being greatly affected by and prolonged in the setting of poor kidney function. Variations in half-life may be partially attributable to

genetics. Some research has suggested the half-life of clonidine is dose dependent and approximately doubles upon chronic dosing, while other work contradicts this. Following a 0.3 mg oral dose, a small study of five patients by Dollery et al (1976) found half-lives ranging between 6.3 - 23.4 hours (mean 12.7). A similar N=5 study by Davies et al. (1977) found a narrower range of half-lives, between 6.7 - 13 hours (average 8.6 hours), while an N=8 study by Keraäen et al. that included younger patients found a somewhat shorter average half-life of 7.5 hours.

History

Clonidine was introduced in 1966. It was first used as a hypertension treatment under the trade name of Catapres.

Society and culture

Brand names

As of June 2017, clonidine was marketed under many brand names worldwide: Arkamin, Aruclonin, Atensina, Catapin, Catapres, Catapresan, Catapressan, Chianda, Chlofazoline, Chlophazolin, Clonid-Ophtal, Clonidin, Clonidina, Clonidinã, Clonidine, Clonidine hydrochloride, Clonidinhydrochlorid, Clonidini, Clonidinum, Clonigen, Clonistada, Clonnirit, Clophelinum, Dixarit, Duraclon, Edolglau, Haemiton, Hypodine, Hypolax, Iporel, Isoglaucon, Jenloga, Kapvay, Klofelino, Kochaniin, Lonid, Melzin, Menograine, Normopresan, Paracefan, Pinsanidine, Run Rui, and Winpress. It was marketed as a

combination drug A combination drug or a fixed-dose combination (FDC) is a medicine that includes two or more active ingredients combined in a single dosage form. Terms like "combination drug" or "combination drug product" can be common shorthand for a FDC prod ...

with

chlortalidone Chlortalidone, also known as chlorthalidone, is a thiazide-like diuretic drug used to treat high blood pressure, swelling including that due to heart failure, liver failure, and nephrotic syndrome, diabetes insipidus, and renal tubular aci ...

as Arkamin-H, Bemplas, Catapres-DIU, and Clorpres, and in combination with

bendroflumethiazide Bendroflumethiazide, formerly bendrofluazide, trade name Aprinox, is a thiazide diuretic used to treat hypertension. Bendroflumethiazide is a thiazide diuretic which works by inhibiting sodium reabsorption at the beginning of the distal convolut ...

as Pertenso.

References

External links

* * Alpha-2 agonists i
ADHD
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Medical uses

Resistant hypertension

Attention deficit hyperactivity disorder

Drug withdrawal

Spasticity

Other uses

Clonidine suppression test

Pregnancy and breastfeeding

Adverse effects

Withdrawal

Pharmacology

Mechanism of action

High blood pressure

Attention deficit hyperactivity disorder

Growth hormone test

Pharmacokinetics

History

Society and culture

Brand names

See also

References

External links