The long-term effects of clonazepam can include depression,  disinhibition, and sexual dysfunction. .
Benzodiazepines do not replace GABA, but instead enhance the effect of GABA at the GABA A receptor by increasing the opening frequency of chloride ion channels, which leads to an increase in GABA's inhibitory effects and resultant central nervous system depression.  In addition, clonazepam decreases the utilization of 5-HT (serotonin) by neurons   and has been shown to bind tightly to central-type benzodiazepine receptors.  The anticonvulsant properties of benzodiazepines are due to the enhancement of synaptic GABA responses, and the inhibition of sustained, high-frequency repetitive firing. Clonazepam's primary mechanism of action is the modulation of GABA function in the brain, by the benzodiazepine receptor, located on GABA A receptors, which, in turn, leads to enhanced GABAergic inhibition of neuronal firing.  Because clonazepam is effective in low milligram doses (0.5 mg clonazepam = 10 mg diazepam),  it is said to be among the class of "highly potent" benzodiazepines. .
Overdose symptoms may include extreme drowsiness, confusion, muscle weakness, and fainting. .
The central nervous system depressing effects of the drug can be intensified by alcohol consumption, and therefore alcohol should be avoided while taking this medication. Clonazepam, like other benzodiazepines, may impair a person's ability to drive or operate machinery. Patients dependent on clonazepam should be slowly titrated off under the supervision of a qualified healthcare professional to reduce the intensity of withdrawal or rebound symptoms. Benzodiazepines have been shown to cause dependence.
Azole antifungals, such as ketoconazole, may inhibit the metabolism of clonazepam.  Clonazepam may affect levels of phenytoin (diphenylhydantoin). Clonazepam decreases the levels of carbamazepine,   and, likewise, clonazepam's level is reduced by carbamazepine.  Clonazepam increases the levels of primidone  and phenobarbital.     In turn, Phenytoin may lower clonazepam plasma levels by increasing the speed of clonazepam clearance by approximay 50% and decreasing its half-life by 31%. .
. Combined use of clonazepam with certain antidepressants, antiepileptics, such as phenobarbital, phenytoin and carbamazepine, sedative antihistamines, opiates, antipsychotics, nonbenzodiazepine hypnotics like zolpidem and alcohol may result in enhanced sedative effects.
.  It begins having an effect within an hour and lasts between 6 and 12 hours. Clonazepam, sold under the brand name Klonopin among others, is a medication used to prevent and treat seizures, panic disorder, and for the movement disorder known as akathisia.  It is a tranquilizer of the benzodiazepine class.  It is taken by mouth.
Of anticonvulsant drugs, behavioural disturbances occur most frequently with clonazepam and phenobarbital. Clonazepam is not recommended for use in those under 18.  . Use in very young children may be especially hazardous.
 .  The wholesale cost in the developing world is between US$ 0.01 and US$0.07 per pill. Clonazepam was initially patented in 1964 and went on sale in 1975 in the United States from Roche.  In many areas of the world it is commonly used as a recreational drug.  In the United States, the pills are about US$0.40 each.  It is available as a generic medication.
Clonazepam may aggravate hepatic porphyria.  .
Common side effects include sleepiness, poor coordination, and agitation.  Dependence occurs in one-third of people who take clonazepam for longer than four weeks.   If used during pregnancy it may result in harm to the baby.  Clonazepam binds to GABA A receptors and increases the effect of the chief inhibitory neurotransmitter gamma -Aminobutyric acid (GABA).  Long-term use may result in tolerance, dependence, and withdrawal symptoms if stopped abruptly.  It may increase risk of suicide in people who are depressed. .
There is some medical evidence of various malformations, e.g., cardiac or facial deformations when used in early pregnancy; however, the data is not conclusive. Withdrawal symptoms from benzodiazepines in the neonate may include hypotonia, apnoeic spells, cyanosis and impaired metabolic responses to cold stress. . Clonazepam, when used late in pregnancy, may result in the development of a severe benzodiazepine withdrawal syndrome in the neonate. The data are also inconclusive on whether benzodiazepines such as clonazepam cause developmental deficits or decreases in IQ in the developing fetus when taken by the mother during pregnancy.
It is effective for 6–8 hours in children, and 6–12 in adults. .
The use of clonazepam during pregnancy should only occur if the clinical benefits are believed to outweigh the clinical risks to the fetus. Possible adverse effects of use of benzodiazepines such as clonazepam during pregnancy include: miscarriage, malformation, intrauterine growth retardation, functional deficits, floppy infant syndrome, carcinogenesis and mutagenesis. Neonatal withdrawal syndrome associated with benzodiazepines include hypertonia, hyperreflexia, restlessness, irritability, abnormal sleep patterns, inconsolable crying, tremors or jerking of the extremities, bradycardia, cyanosis, suckling difficulties, apnea, risk of aspiration of feeds, diarrhea and vomiting, and growth retardation. In many cases, non-pharmacological treatments, such as relaxation therapy, psychotherapy and avoidance of caffeine, can be an effective and safer alternative to the use of benzodiazepines for anxiety in pregnant women. The pathway by which clonazepam is metabolized is usually impaired in newborns. If clonazepam is used during pregnancy or breast feeding, it is recommended that serum levels of clonazepam are monitored and that signs of central nervous system depression and apnea are also checked for. The safety profile of clonazepam during pregnancy is less clear than that of other benzodiazepines, and if benzodiazepines are indicated during pregnancy, chlordiazepoxide and diazepam may be a safer choice. This syndrome can develop between 3 days to 3 weeks after birth and can have a duration of up to several months. . Caution is also required if clonazepam is used during breastfeeding.
 Clonazepam passes through the blood–brain barrier easily, with blood and brain levels corresponding equally with each other. Clonazepam is largely bound to plasma proteins.  .  The metabolites of clonazepam include 7-aminoclonazepam, 7-acetaminoclonazepam and 3-hydroxy clonazepam.
Excess doses may result in:
Klonopin 1 mg tablet.
Clonazepam, like other benzodiazepines, while being a first-line treatment for acute seizures, is not suitable for the long-term treatment of seizures due to the development of tolerance to the anticonvulsant effects.
Benzodiazepines also require special precaution if used by individuals that may be pregnant, alcohol- or drug-dependent, or may have comorbid psychiatric disorders.  Clonazepam is generally not recommended for use in elderly people for insomnia due to its high potency relative to other benzodiazepines. . The elderly are especially susceptible to increased risk of harm from motor impairments and drug accumulation side effects.
. It differs from other anticonvulsant drugs it was compared to in a study. Benzodiazepines do not have any effect on the levels of GABA in the brain.  Clonazepam has no effect on GABA levels and has no effect on gamma-aminobutyric acid transaminase. Clonazepam does, however, affect glutamate decarboxylase activity.
Both the parent drug and 7-aminoclonazepam are unstable in biofluids, and therefore specimens should be preserved with sodium fluoride, stored at the lowest possible temperature and analyzed quickly to minimize losses. . Clonazepam and 7-aminoclonazepam may be quantified in plasma, serum or whole blood in order to monitor compliance in those receiving the drug therapeutically. Results from such tests can be used to confirm the diagnosis in potential poisoning victims or to assist in the forensic investigation in a case of fatal overdosage.
Doses higher than 0.5–1 mg per day are associated with significant sedation. .
 Many individuals treated on a long-term basis develop a dependence.  Use of alcohol or other CNS depressants while taking clonazepam greatly intensifies the effects (and side-effects) of the drug. Physiological dependence was demonstrated by flumazenil -precipitated withdrawal. Benzodiazepines such as clonazepam can be very effective in controlling status epilepticus, but, when used for longer periods of time, some potentially serious side-effects may develop, such as interference with cognitive functions and behavior.
[ citation needed ]. Clonazepam is available as tablets and orally disintegrating tablets (wafers) an oral solution (drops), and as a solution for injection or intravenous infusion.
Clonazepam was the second most frequently implicated benzodiazepine in ED visits. . A 2006 US government study of emergency department (ED) visits found that sedative-hypnotics were the most frequently implicated pharmaceutical drug in ED visits, with benzodiazepines accounting for the majority of these. The criteria for non-medical use in this study were purposefully broad, and include, for example, drug abuse, accidental or intentional overdose, or adverse reactions resulting from legitimate use of the medication. The study examined the number of times the non-medical use of certain drugs was implicated in an ED visit. Alcohol alone was responsible for over twice as many ED visits than clonazepam in the same study.
 Benzodiazepines inhibit cold-induced thyroid stimulating hormone (also known as TSH or thyrotropin) release.   Clonazepam decreases release of acetylcholine in the feline brain  and decreases prolactin release in rats. .  Benzodiazepines acted via micromolar benzodiazepine binding sites as Ca2+ channel blockers and significantly inhibit depolarization-sensitive calcium uptake in experimentation on rat brain cell components. This has been conjectured as a mechanism for high-dose effects on seizures in the study. Benzodiazepines, including clonazepam, bind to mouse glial cell membranes with high affinity.
This further results in an inhibition of synaptic transmission across the central nervous system.  . Clonazepam acts by binding to the benzodiazepine site of the GABA receptors, which enhances the electric effect of GABA binding on neurons, resulting in an increased influx of chloride ions into the neurons.
Doses for the elderly are recommended to be about half of that given to younger adults and are to be administered for no longer than two weeks. Long-acting benzodiazepines such as clonazepam are not generally recommended for the elderly due to the risk of drug accumulation. The elderly metabolize benzodiazepines more slowly than younger individuals and are also more sensitive to the effects of benzodiazepines, even at similar blood plasma levels. .
Clonazepam has similar effectiveness to other benzodiazepines at often a lower dose. .
. Clonazepam is a chlorinated derivative of nitrazepam.
. The effectiveness of clonazepam in the short-term treatment of panic disorder has been demonstrated in controlled clinical trials. [ citation needed ] Clonazepam is also effective in the management of acute mania. Some long-term trials have suggested a benefit of clonazepam for up to three years without the development of tolerance but these trials were not placebo -controlled.
Clonazepam is lipid-soluble, rapidly crosses the blood–brain barrier, and penetrates the placenta. .  Peak blood concentrations of 6.5–13.5 ng/mL were usually reached within 1–2 hours following a single 2 mg oral dose of micronized clonazepam in healthy adults.  It has an elimination half-life of 19–60 hours. It is extensively metabolised into pharmacologically inactive metabolites. Clonazepam is metabolized extensively via nitroreduction by cytochrome P450 enzymes, including CYP3A4. Erythromycin, clarithromycin, ritonavir, itraconazole, ketoconazole, nefazodone, cimetidine, and grapefruit juice are inhibitors of CYP3A4 and can affect the metabolism of benzodiazepines. In some individuals, however, peak blood concentrations were reached at 4–8 hours.
Abrupt or over-rapid withdrawal from clonazepam may result in the development of the benzodiazepine withdrawal syndrome, causing psychosis characterised by dysphoric manifestations, irritability, aggressiveness, anxiety, and hallucinations.    Sudden withdrawal may also induce the potentially life-threatening condition, status epilepticus.  Carbamazepine has been tested in the treatment of clonazepam withdrawal but was found to be ineffective in preventing clonazepam withdrawal-induced status epilepticus from occurring. Anti-epileptic drugs, benzodiazepines such as clonazepam in particular, should be reduced in dose slowly and gradually when discontinuing the drug to mitigate withdrawal effects. .
Klonopin 0.5 mg tablet.
Clonazepam is not recommended for patients with chronic schizophrenia. A 1982 double-blinded, placebo-controlled study found clonazepam increases violent behavior in individuals with chronic schizophrenia. .
amobarbital, at prescribed doses has resulted in a synergistic potentiation of the effects of each drug, leading to serious respiratory depression.  The combination of clonazepam and certain barbiturates, e.g. . Coma can be cyclic, with the individual alternating from a comatose state to a hyper-alert state of consciousness, which occurred in a 4-year-old boy who suffered an overdose of clonazepam.
 Clonazepam is mainly prescribed for the acute management of epilepsies. Clonazepam has been found effective in treating epilepsy in children, and the inhibition of seizure activity seemed to be achieved at low plasma levels of clonazepam. Clonazepam has been found to be effective in the acute control of non-convulsive status epilepticus ; however, the benefits tended to be transient in many of the people, and the addition of phenytoin for lasting control was required in these patients. .  As a result, clonazepam is sometimes used for certain rare childhood epilepsies; however, it has been found to be ineffective in the control of infantile spasms.
 Many studies have found that tolerance develops to the anticonvulsant properties of clonazepam with chronic use, which limits its long-term effectiveness as an anticonvulsant. Tolerance to the anticonvulsant effects of clonazepam occurs in both animals and humans. The degree of tolerance is more pronounced with clonazepam than with chlordiazepoxide. .  In general, short-term therapy is more effective than long-term therapy with clonazepam for the treatment of epilepsy.   Chronic use of benzodiazepines can lead to the development of tolerance with a decrease of benzodiazepine binding sites. In humans, tolerance to the anticonvulsant effects of clonazepam occurs frequently.
. A recurrence of symptoms of the underlying disease should be separated from withdrawal symptoms.
Plasma levels of clonazepam can vary as much as tenfold between different patients.  Clonazepam plasma levels are very unreliable amongst patients. . Clonazepam passes rapidly into the central nervous system, with levels in the brain corresponding with levels of unbound clonazepam in the blood serum.
[ citation needed ]. It is marketed under the trade name Rivotril by Roche in Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Colombia, Costa Rica, Croatia, the Czech Republic, Denmark, Germany, Hungary, Ireland, Italy, China, Mexico, the Netherlands, Norway, Portugal, Peru, Romania, South Africa, Spain, Turkey, and the United States; Emcloz, Linotril and Clonotril in India, South Korea, and other parts of Europe; under the name Riklona in Indonesia and Malaysia; and under the trade name Klonopin by Roche in the United States. Other names, such as Clonoten, Ravotril, Rivatril, Rivotril, Iktorivil, Clonex, Paxam, Petril, Naze and Kriadex, are known throughout the world.
It is also approved for treatment of typical and atypical absences, infantile myoclonic, myoclonic and akinetic seizures.  A subgroup of people with treatment resistant epilepsy may benefit from long-term use of clonazepam; the benzodiazepine clorazepate may be an alternative due to its slow onset of tolerance. .
 Rapid eye movement behavior disorder responds well to low doses of clonazepam. Restless legs syndrome can be treated using clonazepam as a third-line treatment option as the use of clonazepam is still investigational. .   Bruxism also responds to clonazepam in the short-term.
Increasing the dose can overcome the effects of tolerance, but tolerance to the higher dose may occur and adverse effects may intensify. . A gradual reduction in dosage reduces the severity of the benzodiazepine withdrawal syndrome. Withdrawal seizures and psychosis can occur in severe cases of withdrawal, and anxiety and insomnia can occur in less severe cases of withdrawal. High dosage and long-term use increase the risk and severity of dependence and withdrawal symptoms. The mechanism of tolerance includes receptor desensitization, down regulation, receptor decoupling, and alterations in subunit composition and in gene transcription coding. Due to the risks of tolerance and withdrawal seizures, clonazepam is generally not recommended for the long-term management of epilepsies.   One-third of individuals treated with benzodiazepines for longer than four weeks develop a dependence on the drug and experience a withdrawal syndrome upon dose reduction. Like all benzodiazepines, clonazepam is a GABA-positive allosteric modulator.
Clonazepam was approved in the United States as a generic drug in 1997 and is now manufactured and marketed by several companies.
Clonazepam is prescribed for epilepsy and panic disorder with or without agoraphobia.  .
Klonopin 2 mg tablet ∗ Clonazolam.Klonopin