Pharmacological studies with endogenous enhancer substances: beta-phenylethylamine, tryptamine, and their synthetic derivatives.
The discovery of enhancer regulation in the mesencephalon and the concept that it plays a key role in the operation of innate and acquired drives [Neurochem. Res. 28 (2003) 1187] sets the trace amines (TAs) in their true physiological perspective. The regulation is defined as the existence of enhancer-sensitive neurons in the brain capable of working in a split-second on a high activity level due to endogenous enhancer substances. For the time being, only beta-phenylethylamine (PEA) and tryptamine are the experimentally analyzed examples. (-)-Deprenyl (selegiline), widely used in Parkinson's disease and Alzheimer's disease today, and known as the first selective monoamine oxidase (MAO) type-B inhibitor for decades, was identified as a PEA-derived synthetic mesencephalic enhancer substance. An important and convincing confirmation of the enhancer concept was the recent development of a highly specific and potent tryptamine-derived synthetic mesencephalic enhancer substance, (-)-1-(benzofuran-2-yl)-2-propylaminopentane [(-)-BPAP]. This substance, which is specific and hundreds of times more potent than selegiline, is now the best experimental tool to study the enhancer regulation in the mesencephalon and a promising candidate to significantly surpass the therapeutic efficiency of selegiline in depression, Parkinson's disease, and Alzheimer's disease.
Shimazu
Seiichiro
S
Research Institute, Fujimoto Pharmaceutical Corporation, 1-3-40 Nishiotsuka, Matsubara, Osaka 580-0011, Japan. soyaku@fujimoto-pharm.co.jp
Miklya
Ildikó
I
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001572:Benzofurans / Q000494:pharmacology; D006801:Humans; D008636:Mesencephalon / Q000502:physiology; D009422:Nervous System Diseases / Q000188:drug therapy / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D010627:Phenethylamines / Q000737:chemistry*; D011619:Psychotropic Drugs / Q000737:chemistry* / Q000494:pharmacology*; D012642:Selegiline / Q000494:pharmacology; D014363:Tryptamines / Q000737:chemistry / Q000502:physiology*
C404200:1-(benzofuran-2-yl)-2-propylaminopentane; D000928:Antidepressive Agents; D001572:Benzofurans; D018696:Neuroprotective Agents; D010627:Phenethylamines; D011619:Psychotropic Drugs; D014363:Tryptamines; D012642:Selegiline