Neurochemical tools

Structure. The availability of (+)-dihydrothebainone, later accomplished with better procedures (lijima et al. 1978a), made it possible to investigate several unnatural (+)-opioids as neurochemical tools (Jacquet et al. 1977, lijima et al. 1978b). It is interesting to note that sinomenine, only recently tested in an antitussive screen (Nakamura personal communication) proved superior to dextromethorphan and codeine, suggesting that antitussive agents may still be discovered in the (+)-series of mor-phinan alkaloids (Kerekes et al. in press). 

The in vivo microdialysis procedure has corroborated many theories of memory function that were derived originally from studies examining the effects of drugs or lesions on behavioral measures of memory. In vivo microdialysis has provided neurochemical correlates of memory and has also proven to be a useful tool for studying pharmacological interactions within and between brain areas during memory-related processes. 

Pharmacology has provided powerful tools to characterize the neurochemical pathways of stress and anxiety in the brain, and how these pathways are involved in the pathophysiology and treatment of anxiety disorders. In the past, this work has largely focused on classical neurotransmitter systems, including the synthesis, release, and metabolism of monoamines and receptor subtypes that control presynaptic release of neurotransmitters and their postsynaptic effects. Increasing the specihcity of drugs but also the combination of mechanisms has been pursued to improve anxiolytic drugs. 

Thus, there were serotonin 1 receptors, and then there were 1 and 2 receptors, and then la and lb and 2a and 2b receptors, and on and on. These are called 5-HT receptors, since the chemical name for serotonin is 5-hy-droxytryptamine, and the scientist would never want to let the layman know just what he is talking about. DOI has been synthesized with a variety of radioactive iodine isotopes in it, and these tools have been of considerable value in mapping out its brain distribution. And by extrapolation, the possible localization of other psychedelic compounds that cannot be so easily labelled. A small neurochemical research company on the East Coast picked up on these properties of DOI, and offered it as a commercial item for research experiments. But I doubt that they are completely innocent of the fact that DOI is an extremely potent psychedelic and that it is still unrecognized by the Federal drug laws since, in their most recent catalog, the price had almost doubled and a note had been added to the effect that telephone orders cannot be accepted for this compound. 

Zoccarato, F., Cavallini, L., and Alexandre, A. (1999). The pH-sensitive dye acridine orange as a tool to monitor exocytosis/endocytosis in synaptosomes. J. Neurochem. 72, 625-633. 

Bymaster FP, McKinzie DL, Felder CC, Wess J. 2003. Use of M1-M5 muscarinic receptor knockout mice as novel tools to delineate the physiological roles of the muscarinic cholinergic system. Neurochem Res 28 437-442. 

Neurotoxins fi om snake venoms have proved to be valuable tools for the understanding of synaptic transmission mechanisms. Likewise, the powerful inhibitory action of fasciculins against mammalian AChE makes them potentially useful tools for pharmacological and neurochemical research. Studies of their biochemical and elec-trophysiological effects on the central nervous system and biochemical characterization are now being carried out. 

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