This page contains additional details information, clinical trials and research data pertaining to the ingredient Aniracetam found in More Natural Energy™, as well as its related chemical forms. You may print this page for your records if you wish.
The nootropic properties of aniracetam have been the subject of extensive animal research. The research up until 1994 was summarized by Gouliaev and Senning [1]. In tests categorized as "tests of learning," aniracetam prevented or reduced the negative effects of scopolamine and hypoxia in rats and scopolamine in monkeys. In maze tests, aniracetam prevented or reduced the negative effects of scopolamine and basal forebrain lesions in rats and scopolamine and electroconvulsive shock in mice. In passive avoidance tests, aniracetam prevented or reduced the amnestic effect of bicuculline, scopolamine, clonidine, diethyldithiocarbamate, potassium ethylxanthogenate, electroconvulsive shock, and hypoxia in rats and cycloheximide and hypoxia in mice. In an active avoidance test, aniracetam reversed the amnestic effects of clonidine in rats. An experiment is also described in which aniracetam prevented the lethal effect of hemicholinium-3.

Other animal studies have found aniracetam to block the amnestic effect of 6-hydroxydopamine, ischemia, methamphetamine treatment, apomorphine, low-intensity electromagnetic fields, motion sickness, fetal alcohol syndrome, aging, and alprazolam [5-11]. In addition to the animals mentioned above, memory enhancement has been observed in gerbils and pigeons, but in the second case the improvement was not statistically significant [12-13]. Some of the tests in which aniracetam is effective are the two-lever choice reaction task, the radial maze (which tests working memory and spatial memory), the Y-maze, and object recognition (which tests episodic memory) [14-16]. In a study that compared various doses of piracetam and aniracetam, piracetam was only active in six of the nine tests used while aniracetam was active in all of them. And, aniracetam was approximately ten times as potent [17].

There have also been a number of studies on healthy adult or young animals, with either positive or equivocal results. Gouliaev and Senning reference studies showing aniracetam to improve learning in healthy monkeys, as well as studies showing it to improve passive avoidance, learning, and maze performance in healthy rats at dosages ranging from 30-50 mg/kg i.p. and 12.5-800 mg/kg orally [1]. Other literature has commented on aniracetam's ability to improve cognitive function in healthy animals [18].

Of particular interest is the research of Thompson et al. using patas monkeys [5]. They found that aniracetam did not improve cognition in monkeys on a conventional test of learning, but did cause an improvement when they increased the complexity of the task. This increased the total number of errors, but also amplified the difference in performance between control and aniracetam-treated monkeys. Similarly, another study found better results could be achieved in either old rats or young/adult rats depending on the test used [19]. This indicates that the conventional tests may often not be complex enough for aniracetam to offer a statistically significant improvement in healthy animals, which may be the reason for some of the negative results.

Aside from improving learning and memory, aniracetam has a variety of other cognitive effects in animals. Aniracetam provides a significant benefit in multiple animal models of depression and anxiety, such as the forced swim test, the reduction of submissive behavior model, the social interaction test, the elevated plus-maze, and conditioned fear stress [11, 20-21]. The forced swim test is commonly used to screen for compounds with antidepressant properties, while some of the other tests mentioned are used as indicators of compounds that may be useful for the treatment of social phobia, panic anxiety, and generalized anxiety [21]. One study found aniracetam to be superior to piracetam in a model of depression [20].

Aniracetam also improves experimentally-induced deficits in attention and vigilance and improves age-related deficits in temporal regulation of behavior [11]. It was found to increase motivation in animals, as evidenced by increased performance on a task to find food despite satiation, without differences in food intake [22]. In stroke-prone spontaneously hypertensive rats (SHRSP), used as a model of multiple cerebral infarction, aniracetam improves REM sleep [23].

Aniracetam (1-(p-anisoyl)-2-pyrrolidinone, Draganon, Memodrin, Sarpul/Sarple, Ampamet, Reset) was first reported as a nootropic in 1979, and this was followed by a large amount of research in both animals and humans [1]. In 1993, aniracetam was first introduced into clinical practice [2]. Research on aniracetam has also contributed greatly to one of the newer developments in nootropics; namely, it has lead to the creation of the ampakines, and in-depth studies into their mechanisms of action. Aniracetam is a licensed drug in both Italy and Switzerland. It was recently withdrawn in Japan after the publication of a negative study [3]. Like piracetam, oxiracetam, and pramiracetam, aniracetam contains the pyrrolidinone nucleus, but unlike these drugs, it does not contain an acetamide group [4].

Aniracetam’s main use, as supported by the research, is for the treatment of mild to moderate dementia of vascular origin [12, 24-25]. Three studies have shown it to have positive effects in patients with Alzheimer's, and it improved the condition of patients with brainstem infarction [18, 26]. Some of the studies in elderly populations are summarized by Mondadori [27]. One six-month study found that aniracetam treatment caused improvement in all 18 parameters measured, while another study of the same duration found that it caused improvement in 17 of 18 tests, while piracetam treatment caused no change on a number of these tests. Some trials have failed to find a benefit from aniracetam treatment [28].

Aniracetam does not just improve scores on tests of learning and memory. It also affects many other variables. In patients with Alzheimer's, Parkinson's, and cerebral infarction, aniracetam reduces anxiety, depression, and the incidence of sleep disorders, and it has also been reported to improve vigilance [22]. It is also very effective in treating post-stroke depression and sleep disorders [22, 29].

There are no studies concerning the use of aniracetam in healthy, unimpaired humans. However, one study did find it reduced the learning deficits induced by hypoxia in healthy humans [1]. Since piracetam can improve learning and memory in healthy humans, and aniracetam is always superior to piracetam when they are compared, it is presumable that it will have a similar effect, but the degree of this effect is unknown.
Like other nootropics, aniracetam is very safe. The LD50 is 4.5 g/kg orally in rats and 5.0 g/kg orally in mice [1]; for an 80 kg human, this would equate to over 500 times the standard dose of 1.5 g. Animal studies have not found evidence of toxic effects in normal animals, no teratogenic effects have been found, and aniracetam does not influence food intake in rodents [1, 3, 24]. Monkeys do not self-administer aniracetam, and after 31 days of daily dosing, no physical or behavioral withdrawal symptoms are observed upon discontinuation [34].

No drug interactions are known and there are no reported cases of overdose. It is recommended that those with renal insufficiency lower their dose however [24]. In human trials, side effects are rare, but some have been reported, such as insomnia and anxiety. These side effects disappear if the doses are restricted to earlier in the day [24], indicating that they are due to aniracetam’s stimulating effect.

Multiple studies indicate that aniracetam protects against excitotoxicity [3, 12, 36-37], and it also has other neuroprotective effects, such as reducing free radical formation and improving glucose metabolism [38-39]. During conditions of neuronal injury, aniracetam may facilitate the release of inhibitory neurotransmitters [12]. Other compensatory mechanisms may be involved.

1. Gouliaev AH, Senning A. Piracetam and other structurally related nootropics. Brain Res Brain Res Rev. 1994 May;19(2):180-222.

2. Curr Pharm Des. 2002;8(2):125-38. Design and study of piracetam-like nootropics, controversial members of the problematic class of cognition-enhancing drugs. Gualtieri F, Manetti D, Romanelli MN, Ghelardini C.

3. Lancet. 2001 Dec 1;358(9296):1885-92. Pyrrolidone derivatives. Shorvon S.

4. Nootropics – Reviewing the Smart-Drugs. South J.

5. Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7667-71. 7-Chloro-3-methyl-3,4-dihydro-2H-1,2,4-benzothiadiazine S,S-dioxide (IDRA 21), a congener of aniracetam, potently abates pharmacologically induced cognitive impairments in patas monkeys. Thompson DM, Guidotti A, DiBella M, Costa E.

6. Pharmacol Biochem Behav. 1994 Feb;47(2):219-25. Amelioration by aniracetam of abnormalities as revealed in choice reaction performance and shuttle behavior. Himori N, Mishima K.

7. Acta Physiol Pharmacol Bulg. 1993;19(3):77-82. Impairment of learning and memory in shuttle box-trained rats neonatally injected with 6-hydroxydopamine. Effects of nootropic drugs. Stancheva S, Papazova M, Alova L, Lazarova-Bakarova M.

8. Eksp Klin Farmakol. 1996 May-Jun;59(3):20-3. [The nootropic correction of disorders in learning and memory processes induced by extreme exposures] [Article in Russian]. Iasnetsov VV, Krylova IN, Popov VM.

9. Pharmacol Biochem Behav. 1996 Feb;53(2):277-83. Aniracetam restores object recognition impaired by age, scopolamine, and nucleus basalis lesions. Bartolini L, Casamenti F, Pepeu G.

10. Eur Neuropsychopharmacol. 2001 Feb;11(1):33-40. Can nootropic drugs be effective against the impact of ethanol teratogenicity on cognitive performance? Vaglenova J, Vesselinov Petkov V.

11. Pharmacol Biochem Behav. 2002 May;72(1-2):45-53. Cholinergic and dopaminergic mechanisms involved in the recovery of circadian anticipation by aniracetam in aged rats. Tanaka Y, Kurasawa M, Nakamura K.

12. Neurosci Lett. 2003 Mar 27;339(3):187-90. Effects of aniracetam on extracellular levels of transmitter amino acids in the hippocampus of the conscious gerbils: an intracranial microdialysis study. Yu S, Cai J.

13. Pharmacol Biochem Behav. 1985 May;22(5):745-52. Effects of aniracetam on delayed matching-to-sample performance of monkeys and pigeons. Pontecorvo MJ, Evans HL.

14. Brain Res. 2001 Oct 19;916(1-2):211-21. Aniracetam enhances cortical dopamine and serotonin release via cholinergic and glutamatergic mechanisms in SHRSP. Shirane M, Nakamura K.

15. Neurosci Lett. 2001 Feb 9;298(3):183-6. Effects of intrahippocampal aniracetam treatment on Y-maze avoidance learning performance and behavioral long-term potentiation in dentate gyrus in rat. Rao Y, Xiao P, Xu S.

16. Eur J Pharmacol. 2000 Aug 4;401(2):205-12. Effects of S 18986-1, a novel cognitive enhancer, on memory performances in an object recognition task in rats. Lebrun C, Pilliere E, Lestage P.

17. Psychopharmacology (Berl). 1982;78(2):104-11. Effects of the novel compound aniracetam (Ro 13-5057) upon impaired learning and memory in rodents. Cumin R, Bandle EF, Gamzu E, Haefely WE.

18. Pharmacol Biochem Behav. 1997 Jan;56(1):21-9. Effects of D-cycloserine and aniracetam on spatial learning in rats with entorhinal cortex lesions. Zajaczkowski W, Danysz W.

19. Acta Physiol Pharmacol Bulg. 1990;16(2):28-36. Age-related differences in memory and in the memory effects of nootropic drugs. Petkov VD, Mosharrof AH, Petkov VV, Kehayov RA.

20. Eur J Pharmacol. 2002 Apr 5;440(1):27-35. Antidepressant activity of memory-enhancing drugs in the reduction of submissive behavior model. Knapp RJ, Goldenberg R, Shuck C, Cecil A, Watkins J, Miller C, Crites G, Malatynska E.

21. Eur J Pharmacol. 2001 May 18;420(1):33-43. Anxiolytic effects of aniracetam in three different mouse models of anxiety and the underlying mechanism. Nakamura K, Kurasawa M.

22. Pharmacol Biochem Behav. 2001 Jan;68(1):65-9. Aniracetam restores motivation reduced by satiation in a choice reaction task in aged rats. Nakamura K, Kurasawa M.

23. Psychiatry Clin Neurosci. 2000 Jun;54(3):314-6. Effects of aniracetam on impaired sleep patterns in stroke-prone spontaneously hypertensive rats. Kimura M, Okano S, Inoue S.

24. Manufacterer's insert for Draganon.

25. Manufacterer's insert for Ampamet.

26. Auton Neurosci. 2001 Jan 14;86(3):202-7. Autonomic consequences of brainstem infarction. Kihara M, Nishikawa S, Nakasaka Y, Tanaka H, Takahashi M.

27. Mondadori C. Nootropics: preclinical results in the light of clinical effects; comparison with tacrine. Crit Rev Neurobiol. 1996;10(3-4):357-70.

28. Psychopharmacology (Berl). 1987;91(1):90-5. Senile dementia of the Alzheimer type treated with aniracetam: a new nootropic agent. Sourander LB, Portin R, Molsa P, Lahdes A, Rinne UK.

29. Psychopharmacology (Berl). 2001 Nov;158(2):205-12. Antidepressant-like effects of aniracetam in aged rats and its mode of action. Nakamura K, Tanaka Y.

30. J Pharm Sci. 1998 May;87(5):594-8. Pharmacokinetics of aniracetam and its metabolites in rats. Ogiso T, Iwaki M, Tanino T, Ikeda K, Paku T, Horibe Y, Suzuki H.

31. Brain Res Mol Brain Res. 2003 Sep 10;117(1):91-6. 2-pyrrolidinone induces a long-lasting facilitation of hippocampal synaptic transmission by enhancing alpha7 ACh receptor responses via a PKC pathway. Miyamoto H, Yaguchi T, Ohta K, Nagai K, Nagata T, Yamamoto S, Nishizaki T.

32. Behav Brain Res. 1997 Feb;83(1-2):243-4. Pharmacokinetic study of aniracetam in elderly patients with cerebrovascular disease. Endo H, Tajima T, Yamada H, Igata A, Yamamoto Y, Tsuchida H, Nakashima Y, Suzuki Y, Ikari H, Iguchi A.

33. Methods Find Exp Clin Pharmacol. 1980 Oct;2(5):269-85. Quantitative EEG and psychometric analyses in assessing CNS-activity of Ro 13-5057--a cerebral insufficiency improver. Saletu B, Grunberger J, Linzmayer L.

34. Nippon Yakurigaku Zasshi. 1987 Jan;89(1):33-46. [Drug dependence test on a cerebral insufficiency improver, aniracetam] [Article in Japanese]. Kuwahara A, Kubota A, Hakkei M, Nakamura K.

35. Ann N Y Acad Sci. 2003 May;993:229-75; discussion 287-8. Multiple sclerosis and glutamate. Groom AJ, Smith T, Turski L.

36. Neuropharmacology. 2000 Mar 3;39(5):866-72. Group II metabotropic glutamate receptors are a common target of N-anisoyl-GABA and 1S,3R-ACPD in enhancing ACh release in the prefrontal cortex of freely moving SHRSP. Shirane M, Nakamura K.

37. Eur J Pharmacol. 1995 Mar 14;275(3):311-4. N-methyl-D-aspartate neurotoxicity in hippocampal slices: protection by aniracetam. Pizzi M, Consolandi O, Memo M, Spano P.

38. J Neurol Sci. 1999 Mar 15;164(1):7-12. The effect of aniracetam on cerebral glucose metabolism in rats after lesioning of the basal forebrain measured by PET. Ouchi Y, Kakiuchi T, Okada H, Nishiyama S, Tsukada H.

39. J Pharm Pharmacol. 1995 Mar;47(3):253-8. Aniracetam, a pyrrolidinone-type cognition enhancer, attenuates the hydroxyl free radical formation in the brain of mice with brain ischaemia. Himori N, Suzuki T, Ueno K.

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