Nifoxipam

There is a high incidence of death due to respiratory depression when benzodiazepines are combined with depressants such as opiates, alcohol or other GABAergic substances.

Nifoxipam
Chemical Nomenclature
Common names	Nifoxipam
Systematic name	5-(2-fluorophenyl)-3-hydroxy-7-nitro-1,3-dihydro-2H-1,4-benzodiazepin-2-one
Class Membership
Psychoactive class	Depressant
Chemical class	Benzodiazepine
Routes of Administration
Oral Dosage WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. Threshold < 0.5 mg Light 0.5 - 1 mg Common 1 - 2 mg Strong 2 - 3 mg Heavy 3 mg + Duration Total 12 - 17 hours Onset 45 - 120 minutes

Summary sheet: Nifoxipam

Nifoxipam is a long-lasting psychoactive drug of the benzodiazepine class which produces anxiolytic, sedative, hypnotic, muscle relaxant, anticonvulsant, and amnesic effects. Nifoxipam, like other benzodiazepines, binds to specific sites on the GABAA gamma-amino-butyric acid receptor.

It is classed as a 7-nitrobenzodiazepine and is therefore in the same category as other hypnotic nitrobenzodiazepines such as nitrazepam (7-nitro-1,4-benzodiazepin-2-one), nimetazepam (1-methyl-nitrazepam), flunitrazepam (2'-fluoro,1-methyl-nitrazepam) and ''flurazepam'' (1-(2-diethylamino)ethyl-2'-fluoro-nitrazepam).

Nifoxipam has potential use for the short-term treatment of anxiety, insomnia, acute seizures, and the sedation of hospitalized patients. However, it is currently exclusively sold by online research chemical vendors for use as a recreational psychoactive substance.

Chemistry

Nifoxipam is a drug of the benzodiazepine class. Benzodiazepine drugs contain a benzene ring fused to a diazepine ring, which is a seven membered ring with the two nitrogen constituents located at R₁ and R₄. Nifoxipam, or 3-hydroxydesmethylflunitrazepam, is an active metabolite of flunitrazepam. The benzyl ring of nifoxipam is substituted at R₇ with a nitro group, NO₂-. AR₂flourine substituted phenyl ring is bound to this structure at R₅. Additionally, nifoxipam contains a hydroxy (OH-) group substituted at R₃. Nifoxipam also contains an oxygen group double bonded to R₂ of its diazepine ring to form a ketone. This oxygen substitution at R₂ is shared with benzodiazepine drugs with the suffix -azepam. As with flunitrazepam, nifoxipam is likely insoluble in water, although the addition of a hydroxyl group may increase water solubility.

Pharmacology

Benzodiazepines produce a variety of effects by binding to the benzodiazepine receptor site and magnifying the efficiency and effects of the neurotransmitter gamma aminobutyric acid (GABA) by acting on its receptors. As this site is the most prolific inhibitory receptor within the brain, its modulation results in the sedating (or calming effects) of nifoxipam on the nervous system.

Subjective effects

The effects listed below are based upon the subjective effects index and personal experiences of PsychonautWiki contributors. The listed effects will rarely (if ever) occur all at once, but heavier dosages will increase the chances and are more likely to induce a full range of effects.

Physical effects

The physical effects of nifoxipam can be broken down into several components which progressively intensify proportional to dosage. These are described below and generally include:

• Sedation - In terms of energy level alterations, nifoxipam is moderately sedating and can potentially result in a lethargic state. At higher levels, this causes users to suddenly feel as if they are extremely sleep deprived and have not slept for days, forcing them to sit down and generally feel as if they are constantly on the verge of passing out instead of engaging in physical activities. This sense of sleep deprivation increases proportional to dosage and eventually becomes powerful enough to force a person into complete unconsciousness.
• Motor control loss - Lack of coordination may result in falls and injuries, in particular, in the elderly. Another result of motor control loss is the impairment of driving skills and the increased likelihood of road traffic accidents.
• Muscle relaxation
• Dizziness
• Respiratory depression

Cognitive effects

The cognitive effects of nifoxipam can be broken down into several components which progressively intensify proportional to dosage. The general head space of nifoxipam is described by many as one of intense sedation and decreased inhibition. It contains a large number of typical depressant cognitive effects.

The most prominent of these cognitive effects generally include:

• Anxiety suppression
• Thought deceleration
• Disinhibition
• Information processing suppression
• Euphoria
• Amnesia
• Compulsive redosing
• Delusions of sobriety - This is the false belief that one is perfectly sober despite obvious evidence to the contrary such as severe cognitive impairment and an inability to fully communicate with others.

Paradoxical effects

Paradoxical reactions such as increased seizures (in epileptics), aggression, increased anxiety, violent behavior, loss of impulse control, irritability and suicidal behavior sometimes occur (although they are rare in the general population, with an incidence rate below 1%). These paradoxical effects occur with greater frequency in recreational abusers, individuals with mental disorders, children, and patients on high-dosage regimes.

Toxicity and harm potential

Lethal dosage

The lethal dosage of nifoxipam has not been established; however, (like many benzodiazepines) it has a large therapeutic index and margin of safety. Complications may arise when administered in excess. Intentional overdoses have been reported.

As with all GABAergic drugs, overdose can be lethal when mixed with other depressants including alcohol or opioids.

Tolerance and addiction potential

Tolerance will develop to the sedative-hypnotic effects within a couple of days of repeated administration. Abrupt discontinuation of nifoxipam following regular dosing over several days can result in a withdrawal phase which includes rebound symptoms such as increased anxiety and insomnia. It is possible to gradually reduce the dose over the course of several days, which will lengthen the duration of the withdrawal period, but reduce the perceived intensity.

Benzodiazepine discontinuation is notoriously difficult; it is potentially life-threatening for individuals using regularly to discontinue use without tapering their dose over a period of weeks. There is an increased risk of seizure following discontinuation. Drugs which lower the seizure threshold such as tramadol should be avoided during withdrawal.

Dangerous interactions

Although many drugs are safe on their own, they can become dangerous and even life-threatening when combined with other substances. The list below contains some common potentially dangerous combinations, but may not include all of them. Certain combinations may be safe in low doses of each but still increase the potential risk of death. Independent research should always be done to ensure that a combination of two or more substances is safe before consumption.

• Depressants (1,4-Butanediol, 2-methyl-2-butanol, alcohol, barbiturates, GHB/GBL, methaqualone, opioids) - This combination can result in dangerous or even fatal levels of respiratory depression. These substances also potentiate the muscle relaxation, sedation and amnesia caused by one another and can lead to unexpected loss of consciousness at high doses. There is also an increased risk of vomiting during unconsciousness and death from the resulting suffocation. If this occurs, users should attempt to fall asleep in the recovery position or have a friend move them into it.
• Dissociatives - This combination can result in an increased risk of vomiting during unconsciousness and death from the resulting suffocation. If this occurs, users should attempt to fall asleep in the recovery position or have a friend move them into it.
• Stimulants - It is dangerous to combine benzodiazepines with stimulants due to the risk of excessive intoxication. Stimulants decrease the sedative effect of benzodiazepines, which is the main factor most people consider when determining their level of intoxication. Once the stimulant wears off, the effects of benzodiazepines will be significantly increased, leading to intensified disinhibition as well as other effects. If combined, one should strictly limit themselves to only dosing a certain amount of benzodiazepines per hour. This combination can also potentially result in severe dehydration if hydration is not monitored.

Legal issues

Nifoxipam is currently a grey area compound within most (if not all) parts of the world. This means that it is not known to be specifically illegal within any country, but people may still be charged for its possession under certain circumstances such as under analogue laws and with intent to sell or consume.

Preparation methods

Preparation methods for this compound within our preparation index include:

• Volumetric liquid dosing

See also

• Responsible use
• Psychoactive substance index
• Etizolam
• Benzodiazepines
• Depressants