PBN Overview

Alpha Phenyl-N-Tert Butyl Nitrone

PBN is the most extensively researched and widely used Spin Trap

The most commonly used spin trap and the standard which measures new ones is PBN – alpha phenyl-N-tert butyl nitrone. Hundreds of studies have been conducted over the last ten years that have tested PBN and other “spin traps” in numerous conditions.4 Spin traps have been shown to affect cellular oxidation states and oxidatively sensitive enzyme systems.5

  • PBN has been shown to be an excellent neuroprotective and anti-inflammatory agent.6
  • PBN has extended the life span of mice,7 improved cognitive performance in rats,8 reversed protein oxidation in aged gerbils and returned them to youthful states.9
  • PBN has attenuated hydroxyl radical formation in ischemia-reperfusion injury,10 blocked nitric oxide synthase, which minimized the exitotoxicity of peroxynitrite radical.11 Paradoxically, PBN acted as a delivery system for transporting beneficial nitric oxide to targeted areas undergoing oxidative stress.12

Low toxicity

PBN has been shown to be of extremely low toxicity even at the highest dosages and with long-term use.13a,13b The effective dosage of PBN in humans for treating age and ischemic related disorders is expected to be between approximately 1 and 10 mg/70 kg body weight. This equates to 70-700mg for a 70 kg man. Toxicity tests have demonstrated that PBN is completely innocuous, with such low toxicity that it was not possible to determine an LD.sub.50.13c

Spin Traps work differently than antioxidants

Recently, researchers found that the underlying mechanism of “spin trap” activity differs from antioxidants. Spin traps suppress gene transcriptional factors associated with a variety of pathophysiological states.14 In particular, spin traps modulate NF kappa-B regulated cytokines and inducible nitric oxide synthase that are implicated in AIDS, arthritis, arteriosclerosis, Alzheimer’s disease and other pro-inflammatory disease conditions.15 Arguably, this mechanism involves actions at a level proximal to oxidatively sensitive signal amplification systems rather than simple neutralization of free radicals.16

PBN has a wide range of practical applications

Because PBN alters several fundamental cellular processes and metabolic pathways, it may be efficacious for a wide range of conditions. Between the years of 1991 and 2000, researchers, John Carney at University of Kentucky Research Foundation and Robert Floyd at Oklahoma Medical Research Foundation, filed a series of U.S. patents for methods of using PBN. They recommended PBN for many diverse conditions that involve oxidative stress and free-radical pathology.16-23


Aging has been demonstrated to be associated with the production of abnormally high levels of oxidized proteins. The consequence of this increased level of protein oxidation is an abnormally low level of critical enzymes in the affected cells. Most, if not all, cells in the body will undergo abnormally high levels of protein oxidation and there will be decreases in antioxidant systems and abnormally low levels of mitochondrial function. The protein oxidation is thought to arise from oxygen free radicals, largely generated via a metal catalyzed reaction within the cell. Studies have now been conducted that daily administration of a free radical spin trapping compound, PBN, for fourteen days completely reverses this process. Not only is the level of protein oxidation decreased, but the abnormally low level of enzyme activity is restored to normal.

PBN has shown to be efficacious in the process and problems of aging including: Alzheimer’s disease, dementia, Parkinson’s disease, loss of neurotransmitters and receptor sensitivity and macular degeneration.


Multiple in vitro studies have demonstrated that there are a series of biochemical changes that result in the production of free radicals following ischemia. PBN can covalently bind to these radicals and prevent the peroxidation of cellular proteins and fatty acids. The consequence of the trapping of these carbon-centered and oxygen-centered radicals is the termination of the propagation phase of free radical production within the neuron. This interruption of free radical production can decrease the mortality and morbidity seen in strokes.

Central nervous system

PBN has shown to be efficacious in the treatment of concussion, aneurysm, ventricular hemorrhage and associated vasospasm, migraine and other vascular headaches and spinal cord trauma.

Peripheral nervous system

PBN has shown to be efficacious in the treatment of diabetic nerve damage and traumatic nerve damage and disorders arising from ischemia, inflammation and infection.

Diabetic Retinopathy

Diabetes is a disease of abnormal glycation and partial ischemia. Both conditions promote free radical production. The relatively common condition of diabetic retinopathy is thought to involve a microvascular and protein dysfunction of the retina. PBN can limit the glycation mediated production of free radicals and the damage caused by microvascular interruptions.

Burn Treatment and Healing

Healing from serious burns is limited by the inability of the repairing vascular system to supply the rapidly growing cutaneum. Periods of ischemia in the dermis will occur as the growing skin cannot be adequately supplied. This hypoxia or ischemia results in the production of oxygen free radicals and either limits the rate of recovery and/or promotes the generation of scar tissue. Systemic and topical spin-trapping compounds such as PBN can be used to improve the rate of healing and decrease scar formation.

Wound and Ulcer Healing

Tissue healing often involves periods of hypoxia or ischemia as the recovering tissue outgrows the vascular supply. PBN can decrease the damage associated with this period of ischemia.

Other Peripheral organ and tissue disorders

PBN has shown to be efficacious in the treatment of arteriosclerosis, chronic obstructive pulmonary fibrosis, pancreatitis, pulmonary fibrosis due to chemotherapeutic agents, angioplasty, cardiac failure, ischemic bowel disease, bed sores, lupus, ulcerative colitis, organ transplantation, renal hypertension and pulmonary bleeding.

Reduction in Side-effects of Cancer Chemotherapy

A number of cancer chemotherapeutic agents produce their cytotoxic effects via the production of oxygen free radicals within the cell. The limiting side effects of these compounds are also the result of oxygen free radical production in normal cells. Bleomycin produces pulmonary and cutaneous toxicities as a result of hydroxyl free radical production. Adriamycin produces cardiac and gastrointestinal side-effects. PBN has been demonstrated to trap the free radicals produced by adriamycin in heart, brain and other organs of research animals. PBN can be used to limit side effects in tissues, such as the brain and heart, that are especially vulnerable to develop free radicals, without compromising the therapeutic value of the chemotherapeutic agent.

Exertional Injury to Skeletal Muscle

Sore muscles as a result of exercise are thought to be a consequence of free radical mediated peroxidation of skeletal muscle proteins and lipids. Since chronic treatment with spin-trapping compounds decreases cellular oxidations and protects enzymes from oxidative inactivation, daily treatment can be used to improve the process of exercise conditioning (especially in the horse). Moreover, aged skeletal muscle is likely to contain constituents, as do most other cells in the body. Since work has demonstrated that chronic administration of PBN can return cells to the status of a young adult, spin-trapping can be used to improve the functional status and exercise condition of skeletal muscle in aged individuals.

Multi-organ Failure Following Trauma

A characteristic problem following extreme trauma is the development in the patient of a negative nitrogen balance, poor protein synthetic capacity, pulmonary dysfunction, and abnormal cytokine production. Tumor necrosis factor (TNF) is excessively elevated during this process. TNF is associated with the cellular generation of oxygen free radicals in tissue and may be one of the primary causes of this condition. The activation of macrophages and lymphocytes also plays a critical role in the condition. Free radical production by the white cells is part of the process of multiple organ damage. PBN can prevent the propagation phase of this condition and limit the extent of cachexia and organ damage following severe trauma.

Other uses

Pre-surgical treatment to enhance recovery, Human Immunodeficiency Virus (HIV). PBN has also demonstrated value at counteracting serotonin depletion damage from using the recreational drug, MDMA (Ecstasy).24

PBN and alpha-Lipoic Acid were utilized in proving that the mechanism of MDMA neurotoxicity involved free radical attack of the delicate nerve terminals. Both materials administered prior to MDMA exposure either completely blocked or greatly attenuated damage, even at doses significantly higher than those used by humans. This discovery may offer a significant protective benefit to MDMA users.

The wide variety of applications for spin traps has lead to an enormous effort by the pharmaceutical industry to develop new and patentable “spin traps” for use in medicine and diagnostics. Many have been discovered and are in various stages of clinical and pre clinical trials. Still, PBN remains the highest regarded and most extensively tested spin-trapping compound to date.

Dr. Denham Harman, the father of the Free Radical Theory of Aging, and keynote speaker at the 2nd Annual Anti-aging Conference in Monaco, referred to PBN and spin traps as a ‘breakthrough in anti-aging therapy’ with the potential to significantly slow down the aging process.


  1. Nitrone inhibition of age associated oxidative damage. Floyd, R.A. Ann NY Acad Sci 2000; 899:222-37.
  2. Nitrones, their value as therapeutics and probes to understand aging. Floyd RA, Hensley K, et al. Mech Ageing Dev. 2002 Apr30;123(8):1021-31. b) Do Spin Traps also act as classical chain-breaking antioxidants? A quantitative kinetic study of PBN in solution and in liposomes. Free Rad Biol Med 2000 Apr 1; 28 (7) 1079-90
  3. Synthesis and antioxidant efficiency of a new amphiphilic spin-trap derived from PBN and Lipoic Acid. Durand G, Polidori A, Salles JP, Prost M, Durand P, Pucci B. Bioorg Med Chem Lett. 2003 Aug 18;13(16):2673-6. b) Unique in vivo applications of spin traps , Berliner, L.J. et. al. Free Rad Biol Med 2001 Mar 1; 30 (5) :489-99
  4. Pharmacokinetics and metabolism of the reactive oxygen scavenger alpha-phenyl-N-tert-butylnitrone in the male Sprague-Dawley rat. Trudeau-Lame ME, Kalgutkar AS, LaFontaine M. Drug Metab Dispos. 2003 Feb;31(2):147-52.
  5. Nitrone-based free radical traps as neuroprotective agents in cerebral ischaemia and other pathologies. Hensley, K. Int Rev Neurobiol 1997; 40: 299-317
  6. Antioxidants, oxidative stress, and degenerative neurological disorders. Floyd, R.A., Proc Soc Exp Biol Med 1999 Dec; 222 (3) : 236-45 b) Inhibition of NF-kappaB, iNOS mRNA, COX2 mRNA, and COX catalytic activity by PBN.Kotake, Y., Biochim Biophys Acta 1998 Nov 19; 1448 (1): 77-84
  7. A spin trap, PBN extends the life span of mice. Saito, K; Biosci Biotech Biochem 1998 Apr; 62 (4): 792-4
  8. Antioxidant treatment with PBN improves the cognitive performance and survival of aging rats. Sack, C.A.; Neurosci Lett 1996 Mar 1; 205 (3): 181-4
  9. Effect of the spin trapping compound PBN on protein oxidation and life span. Dubey, A., Arch Biochem Biophys 1995 Dec 20: 324 (2): 249-54
  10. PBN attenuates hydroxyl radical production during ischemia-reperfusion injury of rat brain: an EPR study. Sen, S., Free Radic Res Commun 1993: 19 (4) 255-65
  11. In vivo or in vitro administration of the nitrone spin-trapping compound, n-tert-butyl-alpha-phenylnitrone, (PBN) reduces age-related deficits in striatal muscarinic receptor sensitivity.Joseph JA, Cao G, Cutler RC.Brain Res. 1995 Feb 6;671(1):73-7.
  12. Neuroprotective effects of nitrone radical scavenger S-PBN on reperfusion nerve injury in rats. Gray C, Nukada H , Jackson DM, McMorran PD, Wu A , Ma F. Brain Res. 2003 Aug 29;982(2):179-85. b) ESR characterization of a novel spin-trapping agent, 15N-labeled N-tert-butyl-alpha-phenylnitrone, as a nitric oxide donor. Saito K, Yoshioka, H. Biosci Biotechnol Biochem . 2002 Oct;66(10):2189-93. c) Differences in cerebral reperfusion and oxidative injury after cardiac arrest in pigs. Liu XL, Wiklund L, Nozari A, Rubertsson S, Basu S. Acta Anaesthesiol Scand. 2003 Sep;47(8):958-67.
  13. In vitro and in vivo assessment of the irritation potential of different spin traps in human skin. Fuchs J, Groth N , Herrling T. Toxicology. 2000 Oct 26;151(1-3):55-63. b) Cutaneous tolerance to nitroxide free radicals and nitrone spin traps in the guinea pig.Fuchs J, Groth N , Herrling T. Toxicology. 1998 Feb 20;126(1):33-40. c) Carney, J, et al. US Patent Application 20050272724, December 8, 2005.
  14. Increased oxidative stress brought on by pro-inflammatory cytokines in neuro- Degenerative processes and the protective role of nitrone based free radical traps. Floyd R.A.; Life Sci 1999; 65 (18-19): 1893-9 a) Expression of cytokines and activation of transcription factors in lipopolysaccharide-administered rats and their inhibition by PBN. Sang, H., Arch Biochem Biophys 1999 Mar 15; 363 (2): 341-8
  15. Spin trap salvage from endotoxemia: the role of cytokine down-regulation. Surgery. 1992 Aug;112(2):130-9; discussion 138-9. Pogrebniak HW, Merino MJ, Hahn SM, Mitchell JB, Pass HI.
  16. Carney J, et al. United States Patent, 5,578,617 November 26, 1996
  17. Carney J, et al. United States Patent, 6,107,315. August 22, 2000
  18. Carney J, et al. United States Patent, 5,405,874. April 11, 1995
  19. Carney J, et al. United States Patent, 5,025,032. June 18, 1991
  20. Carney J, et al. United States Patent, 5,681,965. October 28, 1997
  21. Carney J, et al. United States Patent, 6,002,001. June 18, 1999
  22. Carney J, et al. United States Patent, 5,622,994. April 22, 1997
  23. Carney J, et al. United States Patent, 5,025,032. June 18, 1991
  24. PBN protects against 3,4-methylenedioxymethamphetamine-induced depletion of serotonin in rats. Yeh, S.Y., Synapse 31:169-177 1999
  25. See the following link for more information: http://www.mcw.edu/frrc/links.htm