Enhancer substances

Flavour enhancer Substance which enhances the existing taste and/or odour of a foodstuff... 

Boyce EG. Use and effectiveness of performance-enhancing substances. J Pharm Pract 2003 16 22-36. 

STREET NAMES Legal steroid, muscle candy, ergogenic aid, performance-enhancing substance DRUG CLASSIFICATIONS Not scheduled, dietary supplement... 

Another large-scale national survey conducted by the Blue Cross and Blue Shield Association s Healthy Competition Foundation in 2001 found that an estimated one million adolescents surveyed (12-17 years of age) had tried performance-enhancing substances such as creatine. In addition, 55% of those surveyed knew someone who took supplements to improve sports performance. 

Friedl KE. Performance-enhancing substance Effects, risks, and appropriate alternatives. In Baechle TR, ed. Essentials of Strength Training and Conditioning. Champaign, IL Human Kinetics, 1994 188-209. 

Though not a natural product, another performance-enhancing substance, Viagra, which is used to treat erectile dysfunction in men, has been suspected of contributing to cardiovascular problems, including heart attacks.)... 

Finally, the data reinforce the proposal (see Knoll, 2001, for review) that prophylactic administration of a synthetic mesencephalic enhancer substance during postdevelopmental life could significantly slow the unavoidable decay of behavioral performances, prolong life, and prevent or delay the onset of age-related neurodegenerative diseases, such as Parkinson s and Alzheimer s. 

We described earlier the essence of both the innate and acquired drives as a state of specific activation (active focus) in a special population of subcortical and cortical neurons, respectively (see Fig. 11 in Knoll 1969). In the light of the enhancer regulation concept, we may characterize the active focus as an endogenous enhancer substance-induced enhanced excitability in a circumscribed population of mesencephalic and telencephalic neurons that persists until the goal has been reached. 

Mesencephalic Enhancer Regulation Natural and Synthetic Mesencephalic Enhancer Substances... 

We can define enhancer regulation as the existence of enhancer-sensitive neurons capable of changing their excitability in a split second and working on a higher activity level, due to natural enhancer substances. Of the agents with such effect, for the time being, only 3-phenylethylamine (PEA) and tryptamine have been experimentally analyzed (Knoll 2001,2003). 

The catecholaminergic and serotonergic neurons in the mesencephalon are excellent models to study the enhancer regulation since their physiological function is to supply the brain continuously with the proper amounts of monoamines that influence - activate or inhibit - billions of neurons. The significant enhancement of the nerve-stimulation-induced release of [3H]-norepinephrine, [3H]-dopamine, and [3H]-serotonin from the isolated brain stem of the rat in the presence of PEA (Fig. 3.1) or tryptamine (Fig. 3.2) is shown to illustrate the response of enhancer-sensitive neurons to endogenous enhancer substances. 

PEA and tryptamine, the first examples of physiological enhancer substances, represent just the peak of an iceberg. The development of a tryptamine-derived synthetic enhancer substance that increased the performance of cul-... 

Further studies clarified the operation of mesencephalic enhancer regulation (Knoll and Miklya 1995 Knoll et al. 1996a,b,c). We realized that PEA, the parent compound of (-)-deprenyl, is primarily an endogenous mesencephalic enhancer substance. Since PEA, in higher concentrations, is a highly effective releaser of catecholamines from their intraneuronal stores, this effect covered up completely the enhancer effect of this endogenous amine, which was classified as the prototype of the indirectly acting sympathomimetics. 

Deprenyl (Selegiline) and / -(-)-1-(benzofuran-2-yl)-2-propylaminopentane [H-BPAP], Prototypes of Synthetic Mesencephalic Enhancer Substances... 

Since (-)-deprenyl is a highly potent and selective inhibitor of MAO-B, we performed a structure-activity relationship study to develop a deprenyl-derived enhancer substance that is free of the MAO-B inhibitory property (Knoll etal. 1992a). (-)-l-Phenyl-2-propylaminopentane [(-)-PPAP] has been chosen as our reference substance with this pharmacological profile. 

The discovery that tryptamine is also an endogenous enhancer substance (Knoll 1994) opened the way for a structure-activity relationship study aiming to synthesize a new family of enhancer compounds structurally unrelated to PEA and the amphetamines. J -(-)-l-(benzofuran-2-yl)-2-propylaminopen-tane [ (-)-BPAP ] was selected as a tryptamine-derived synthetic mesencephalic... 

Figure 3.10 shows the chemical structure and pharmacological spectrum of tryptamine and two of the tryptamine-derived synthetic mesencephalic enhancer substances. 

Enhancer substances stimulate the enhancer-sensitive neurons in the mesencephalon in a peculiar manner. Figure 3.11 shows the characteristics of the enhancer effect of (-)-BPAP added to isolated locus coerulei of rats. We see two bell-shaped concentration/effect curves. The one in the low nanomolar range, with a peak effect at 10 13 M concentration, clearly demonstrates the existence of a highly complex, specific form of enhancer regulation in noradrenergic neurons. The second, with a peak effect at 10-6 M concentration, shows the operation of a ten million times less sensitive, obviously nonspecific form of the enhancer regulation in these neurons (see Knoll et al. 2002b, for details). 

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