•Non-Addictive

•Improve Sleep Latency

•Improve Restorative Sleep

•Improve Autonomic Function

•No Significant AM Grogginess

•Effective as an Adjunct or Standalone

Therapy

Innovative Sleep Solutions

2

Indication & Dosing

Sentra PM® for the dietary management of sleep disorders associated with:• Fibromyalgia• Depression• Dysautonomia• PTSD

Recommended Dosing: 2 capsules QD, 30 minutes before bedtime or as directed by physician.

3

Fall Asleep Faster with Sentra PM®

After a 14 day administration of Sentra PM subjects reported a statistically significant improvement in the time it takes to fall asleep compared to placebo or placebo and trazodone (50mg).*

* Shell, et al. “Sentra PM and Trazodone for the management of Sleep Disorders” Journal of Central Nervous System Disease; 2012:4

4

**p<0.001

n=111

After a 14 day administration of Sentra PM as an adjunct to trazodone (50mg), subjects experienced a statistically significant improvement in quality of sleep compared to placebo, placebo and Sentra PM and placebo and tazodone (50mg).*

* Shell, et al. “Sentra PM and Trazodone for the management of Sleep Disorders” Journal of Central Nervous System Disease; 2012:4

Sentra PM® Effective as an Adjunct Therapy

5

0

1

2

3

4

5

6

7

0.95

1.98

3.86**

6.48**

Improvement in Quality of Sleep

Improvement in Quality of Sleep

Chan

ge in

VAS

10

pt sc

ale

(PSE

Q)

**p<0.001

n=111

After 14 days of administration of Sentra PM and trazodone (50mg), subjects reported a statistically significant reduction in feelings of depression compared to placebo, placebo and Trazodone (50mg), or Sentra PM.*

* Shell, et al. “Sentra PM and Trazodone for the management of Sleep Disorders” Journal of Central Nervous System Disease; 2012:4

Sentra PM® Effective as an Adjunct Therapy

6

-2.5

-2

-1.5

-1

-0.5

0

0.5

1

1.51.13

-0.922**-1.15**

-2.3**

Improvement in Feelings of Depression

Improvement in Feelings of Depression

Chan

ge in

VAS

10

pt S

cale

(PSE

Q)

* p<0.01**p<0.001

n=111

* p<0.01**p<0.001

n=111

After a 14 day administration of Sentra PM or trazodone (50mg) and Sentra PM, subjects experienced a statistically significant improvement in nighttime parasympathetic nervous system activity from midnight to 5am compared to placebo and placebo and trazodone (50mg).** Shell, et al. “Sentra PM and Trazodone for the management of Sleep Disorders” Journal of Central Nervous System Disease; 2012:4

Sentra PM® Improves Nighttime Parasympathetic Function

7

-500

0

500

1000

1500

2000

-125.55-218.11

913.3

1752.65

Change in Nighttime Parasympathetic Activity

Change in Nighttime Parasympathetic Activity

Chan

ge in

Circ

adia

n In

dex

p<0.001n=111

Increased Nutritional Requirements

When physiologic needs are altered by depression, fibromyalgia, or other disorders that increase metabolic demand and disrupt homeostasis, the usual rate of synthesis is no longer sufficient and these amino acids, nutrients, and biogenic amines become conditionally essential. (1-2)

The altered metabolic processes associated with these disease states require additional amounts of glutamine, choline, and tryptophan to address specific nutritional deficiencies.(1-4)

Sentra PM is a source of amino acids, biogenic amines, and other nutrients formulated to address specific nutritional deficiencies in patients with sleep disorders associated with fibromyalgia, depression, dysautonomia and PTSD.

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1. Wurtman RJ. Nutrients affecting brain composition and behavior. Integr Psychiatry 1987;5:226-238. 2. Russell IJ, Michalek JE, Vipraio GA, Fletcher EM, Wall K. Serum amino acids in fibrositis/fibromyalgia syndrome. J Rheumatol Suppl 1989;19:158-163.3. Zeisel SH. Dietary influences on neurotransmission. Adv Pediatr 1986;33:23-47.4. Fernstrom JD. Dietary precursors and brain neurotransmitter formation. Annual Rev Med 1981;32:413-425.

Disordered metabolic processes can alter the balance of nutrient consumption leading to an imbalance in nervous system activity.

Pharmacodynamics

The pharmacodynamic properties of Sentra PM® are directly related to the effects of the amino acid precursors on neurotransmitter activity which are responsible for altering electrical activity in specific areas of the brain that regulate sleep and wake cycles.

The use of Sentra PM in the management of sleep disorders associated with fibromyalgia, depression, and PTSD is supported by experimental and clinical data which have identified specific roles for each ingredient in modulation of pain, mood, autonomic function and the sleep-wake cycle.

Sentra PM is formulated with Targeted Cellular Technology (TCT) a patented integrated molecular system that delivers milligram quantities of amino acids and other ingredients to targeted cells in a time sensitive manner and in specific ratios efficiently promote neurotransmitter production.

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Amino acids and nutrients are precursors to the neurotransmitters that regulate nervous system function.

Why is Sentra PM ® a good choice?

No Reported Adverse Side Effects or Attenuation• No significant morning grogginess*

• No potential for addiction

• No tolerance build up

Effective Non-Addictive Sleep Medication• Reduces sleep latency*

• Increases nighttime parasympathetic autonomic nervous system function*

*Shell, et al. “Sentra PM and Trazodone for the management of Sleep Disorders” Journal of Central Nervous System Disease; 2012:4

Effective Adjunct Therapy• Co-administration with a low dose antidepressant improves feelings of

depression*

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Clinical Applications of Sentra PM®

Replace or Augment Common Sleep Therapies• Hypnotics, SSRIs or other sedatives can be addictive or

have dangerous side effects

• Sentra PM can be administered as an adjunct to a low dose anti-depressant*

• Sentra PM can improve autonomic dysfunction associated with pain syndromes, PTSD and depression

*Shell, et al. “Sentra PM and Trazodone for the management of Sleep Disorders” Journal of Central Nervous System Disease; 2012:4

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Safety Information

PRECAUTIONS AND CONTRAINDICATIONSSentra PM® is contraindicated in an extremely small number of patients with hypersensitivity to any of the nutritional components of Sentra PM.

ADVERSE REACTIONSIngestion of L-Tryptophan, L-Arginine, or Choline at high doses of up to 15 grams daily is generally well tolerated. The most common adverse reactions of higher doses — from 15 to 30 grams daily — are nausea, abdominal cramps, and diarrhea. Sentra PM contains less than 1 gram per dose of amino acids however, some patients may experience these symptoms at lower doses. The total combined amount of amino acids in each Sentra PM capsule does not exceed 400 mg.

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DRUG INTERACTIONSSentra PM® does not directly influence the pharmacokinetics of prescription drugs. Clinical experience has shown that administration of Sentra PM may allow for lowering the dose of co-administered drugs under physician supervision.

OVERDOSEThere is a negligible risk of overdose with Sentra PM as the total amount of amino acids in a one month supply (60 capsules) is less than 20 grams. Overdose symptoms may include diarrhea, weakness, and nausea.

Safety Information

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Select References

1. Fuller PM, Gooley JJ, Saper CB. Neurobiology of the sleep-wake cycle: sleep architecture, circadian regulation, and regulatory feedback. J Biol Rhythms 2006;21:482-493.2. Turek FW, Dugovic C, Zee PC. Current understanding of the circadian clock and the clinical implications for neurological disorders. Arch Neurol 2001;58:1781-1787.3. Gallopin T, Fort P, Eggermann E et al. Identification of sleep-promoting neurons in vitro. Nature 2000;404:992-995.4. Dickenson AH, Chapman V, Green GM. The pharmacology of excitatory and inhibitory amino acid-mediated events in the transmission and modulation of pain in the spinal

cord. Gen Pharmacol 1997;28:633-638.5. Johnston GA. Medicinal chemistry and molecular pharmacology of GABA(C) receptors. Curr Top Med Chem 2002;2:903-913.6. Danneberg P, Weber KH. Chemical structure and biological activity of the diazepines. Br J Clin Pharmacol 1983;16 Suppl 2:231S-244S.7. Moore RY. Suprachiasmatic nucleus in sleep-wake regulation. Sleep Med 2007;8 Suppl 3:27-33.8. Silver R, Lesauter J. Circadian and homeostatic factors in arousal. Ann N Y Acad Sci 2008;1129:263-274.9. Benarroch EE. Suprachiasmatic nucleus and melatonin: reciprocal interactions and clinical correlations. Neurology 2008;71:594-598.10. Zimmermann RC, McDougle CJ, Schumacher M et al. Effects of acute tryptophan depletion on nocturnal melatonin secretion in humans. J Clin Endocrinol Metab 1993;76:1160-

1164.11. Bunney JN, Potkin SG. Circadian abnormalities, molecular clock genes and chronobiological treatments in depression. Br Med Bull 2008;86:23-32.12. Buijs RM, la Fleur SE, Wortel J et al. The suprachiasmatic nucleus balances sympathetic and parasympathetic output to peripheral organs through separate preautonomic

neurons. J Comp Neurol 2003;464:36-48.13. Horner RL. Is there a rationale in modulating brainstem neurons in obstructive sleep apnea and is it clinically relevant? Sleep 2000;23 Suppl 4:S179-S181.14. Markov D, Goldman M. Normal sleep and circadian rhythms: neurobiologic mechanisms underlying sleep and wakefulness. Psychiatr Clin North Am 2006;29:841-853.15. Buckley TM, Schatzberg AF. On the interactions of the hypothalamic-pituitary-adrenal (HPA) axis and sleep: normal HPA axis activity and circadian rhythm, exemplary sleep

disorders. J Clin Endocrinol Metab 2005;90:3106-3114.16. Morin LP. Serotonin and the regulation of mammalian circadian rhythmicity. Ann Med 1999; 31:12-33.17. Gvilia I, Xu F, McGinty D, Szymusiak R. Homeostatic regulation of sleep: a role for preoptic area neurons. J Neurosci 2006;26:9426-9433.18. Hogg RC, Raggenbass M, Bertrand D. Nicotinic acetylcholine receptors: from structure to brain function. Rev Physiol Biochem Pharmacol 2003;147:1-46.19. Martyn JA, Fagerlund MJ, Eriksson LI. Basic principles of neuromuscular transmission. Anaesthesia 2009;64 Suppl 1:1-9.20. Parker AJ, Wessely S, Cleare AJ. The neuroendocrinology of chronic fatigue syndrome and fibromyalgia. Psychol Med 2001;31:1331-1345.21. Neeck G, Crofford LJ. Neuroendocrine perturbations in fibromyalgia and chronic fatigue syndrome. Rheum Dis Clin North Am 2000;26:989-1002.22. Gur A, Oktayoglu P. Central nervous system abnormalities in fibromyalgia and chronic fatigue syndrome: new concepts in treatment. Curr Pharm Des 2008;14:1274-1294.23. Szymusiak R, McGinty D. Hypothalamic regulation of sleep and arousal. Ann N Y Acad Sci 2008;1129:275-286.24. Seifritz E. Contribution of sleep physiology to depressive pathophysiology. Neuropsychopharmacology 2001;25:S85-S88.25. Carlsson A. Interaction between dopaminergic and serotoninergic systems. Clin Neuropharmacol 1992;15 Suppl 1 Pt A:616A-617A.26. Gillin JC, Salin-Pascual R, Velazquez-Moctezuma J, Shiromani P, Zoltoski R. Cholinergic receptor subtypes and REM sleep in animals and normal controls. Prog Brain Res

1993;98:379-387.27. Guha M, Biswas S, Poddar MK. Possible involvement of central cholinergic-serotoninergic interaction in natural sleep. Methods Find Exp Clin Pharmacol 1988;10:243-245.28. Huwig-Poppe C, Voderholzer U, Backhaus J, Riemann D, Konig A, Hohagen F. The tryptophan depletion test. Impact on sleep in healthy subjects and patients with obsessive-

compulsive disorder. Adv Exp Med Biol 1999;467:35-42.29. Fernstrom JD. Effects of the diet and other metabolic phenomena on brain tryptophan uptake and serotonin synthesis. Adv Exp Med Biol 1991;294:369-376.30. Jouvet M. Sleep and serotonin: an unfinished story. Neuropsychopharmacology 1999;21:24S-27S.31. Nitz D, Siegel J. GABA release in the dorsal raphe nucleus: role in the control of REM sleep. Am J Physiol 1997;273:R451-R455.32. Marks GA, Roffwarg HP. The cholinergic influence upon rat dorsal lateral geniculate nucleus is dependent on state of arousal. Brain Res 1989;494:294-306.

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