Alkyl Nitrites
Substance Abuse

Author: Lorenzo Gammino
Date: 28/06/2012


Alkyl Nitrites: recreational drugs known as “poppers”

Lorenzo Gammino
Simone Benedetto


Commonly referred to as "poppers", inhaled alkyl nitrites are rapid-onset, short-acting potent vasodilators that produce a rush characterized by warm sensations, feelings of dizziness and slowed perception of time. They represent a common class of recreational drugs that have a long history of being abused in social settings, particularly among gay and bisexual men. They have been part of the club culture from the 1970s disco scene to the 1980s and 1990s rave scene.
These substances are called "poppers" because the liquid drug was first available in a capsule that was cracked or popped open to release vapors.
They are Isopropyl nitrite, Isobutyl nitrite, Amyl nitrite, Butyl nitrite.


Inhaled nitrites rapidly and effectively are absorbed into the bloodstream, with the onset of effects being in the order of seconds. Subsequently, the nitrites are rapidly metabolized by the liver, kidneys, lungs, intestinal mucosa, and vascular tissue, with effects lasting only minutes. Most of the metabolism occurs hepatically by the enzyme glutathione-organic nitrates reductase. Approximately one-third of the inhaled amyl nitrite is excreted in the urine. (

Molecular mechanism

The nitrites are potent vasodilatory substances. The vasodilatory effects are accomplished by relaxing involuntary muscles of the vasculature thanks to the release of nitric oxide (NO). NO diffuses rapidly into vascular smooth muscles, where it reacts with the haem group of an enzyme, guanylyl cyclase. The activated enzyme catalyses the production of cyclic guanosine monophosphate (cGMP). Cyclic GMP activates protein kinase G, which causes phosphorylation of myosin light chain phosphatase, and therefore inactivation of myosin light-chain kinase, and leads ultimately to the dephosphorylation of the myosin light chain, causing smooth muscle relaxation.

Thanks to this properties Sir Thomas Lauder Brunton (1844–1916), a Scottish physician, famously pioneered the use of amyl nitrite (the first alkyl nitrite to be synthesized) to treat angina pectoris.
After inhalation, vasodilatation often results in temporary reductions in blood pressure accompanied by tachycardia, lightheadedness, and syncopal feelings.
Volatile nitrites are frequently used as an adjunct to sexual behavior; because of their smooth muscle effects, nitrites can reduce sphincter tone, thus facilitating anal intercorse.
Users of nitrites report that the drug enhances sexual perception and pleasure; the rush or high experienced by users is perceveid to augment or intensify sexual orgasm. The head rush, euphoria, and other sensations that result from the increased heart rate are often felt to increase sexual arousal and desire.

Nitrites can enter red blood cells and oxidize hemoglobin, forming methemoglobin. In cases of cyanide toxicity, induction of methemoglobin may actually play a beneficial role by displacing cyanide from the heme group of cytochrome oxidase. (Poppers: epidemiology and clinical management of inhaled nitrite abuse)

Side effects and toxicity

Frequent use of inhaled nitrites is associated with a myriad of adverse effects. Some of these are the following.

  • Potentially life threatening methemglobinemia. Nitrites oxydize haemoglobin forming methemglobin that has a decreased affinity for oxygen, resulting in an increased affinity of oxygen to other heme sites and overall reduced ability to release oxygen to tissues. When methemoglobin concentration is elevated in red blood cells, tissue hypoxia can occurs. The therapy consist in administration of methylen blue.
  • Skin and Tracheobronchial irritation (i.e. crusty lesions, erithema)
  • Sinusitis
  • Allergical reaction accompanied by wheezing and dispnea
  • Transient elevation in intraocular pressure
  • Headache. It is cause by both cerebral vasodilatation and methemglobinemia.
  • Hemolytic anemia in patients deficient in glucose-6-phosphate dehydrogenase (G6PDH); anemia was believed to be caused by oxidative red blood cell stress, elicited by nitrite use and exacerbated by a deficient G6PDH enzyme system.
  • Nausea and vomiting
  • Fainting
  • Decreased blood pressure
    (The Acute Toxicity of Nitrite Inhalants)

Moreover there are some open questions concerning adverse effects of alkyl nitrite.
We still know too little about potential their carcinogenic effect. It is proved that nitrites reacts with endogenous nitrogen compounds to nitrosamine, some of which are known to be carcinogen (i.e. dimethylnitrosamine). (Poppers: epidemiology and clinical management of inhaled nitrite abuse)

“Poppers” are associated with Kaposi’s Sarcoma but it is not clear if there is a biological link between the two. The development of Kaposi’s Sarcoma is extensively linked to VEGF. Acute and chronic in vivo exposure to isobutyl nitrite produced significant tissue dependent alterations in the expression of a number of cancer- and angiogenesis-related genes in mice. In particular, hepatic mRNA and protein expression of vascular endothelial growth factor (VEGF) was significantly stimulated. This can suggest a possible role of Alkyle nitrites in the pathogenesis of the cancer. (Effects of Inhalant Nitrites on VEGF Expression: A Feasible Link to Kaposi’s Sarcoma)

The use of alkyl nitrites is associated with HIV infections for several reason. First of all the relaxation of anal sphincter can facilitate more forceful anal intercourse. Moreover vasodilatation of perianal blood vessels may result in increased blood flow to the anal cavity; given the traumatic nature of anal intercourse, increased blood flow may result in more efficient acquisition of blood-borne diseases such as HIV or hepatitis B.

Pharmacological interactions

Concurrent use of Sildenafil and nitrites may result in lifethreatening hypotension. It is important to remember that recreational drug users often take Sildenafil to counteract the impotence-inducing effects of certain agents (i.e., Ecstasy).

AddThis Social Bookmark Button