Serotonin-like activity

A variety of side-chain modified analogs of MDMA and MBDB have begun to be examined. Very early studies were of the a,a-dimethyl analog, 3,4-methylenedioxyphentermine (figure 8a) and its N-methyl derivative (figure 10). This latter compound proved to lack MDMA-like activity (Shulgin, unpublished). Interestingly, this compound also lacked the ability to stimulate the release of [ H] serotonin from prelabeled rat brain synaptosomes (Nichols et al. 1982). 

This type of action is found in kanna, or Sceletium expansum and Sceletium tortuosum (Aizoaceae), which have been used by South African shamans from prehistoric times to enhance animal spirits, sparkle the eyes, and to stimulate gaiety. The active constituent of kanna is a serotonin-like alkaloid called mesembrine, which is a potent serotonin re-uptake inhibitor—hence, some potential for the treatment of anxiety and depression however, careful clinical trials must be performed. 

Boyle, J.P., Hillyer, J.F. and Yoshino, T.P. (2003b) Pharmacological and autoradiographical characterization of serotonin transporter-like activity in sporocysts of the human blood fluke, Schistosoma mansoni. Journal of Comparative Physiology A Sensory, Neural, and Behavioral Physiology 189, 631-641. 

Chenu F, Guiard BP, Bourin M, Gardier AM. Antidepressant-like activity of selective serotonin reuptake inhibitors combined with 87. a NKl receptor antagonist in the mouse forced swimming test. 

Three separate categories of endogenous substances with morphine-like activity have been identified. These families of neuropeptides are known as enkephalins, endorphins, and dynorphins. Each family is derived from a distinct precursor polypeptide (pro-enkephalin, pro-opiomelanocortin, and prodynorfin) and has a characteristic anatomical distribution. The enkephalins and dynorphins found co-exist with other neurotransmitters, such as serotonin (5-HT) and noradrenaline, but details of how the peptides modulate the activity of co-transmitters await elucidation. 

Several other substances which have hormone-like activity are widely distributed and exert their effects in the area in which they are produced. Histamine, serotonin and various plasma kinins may be considered to be local hormones. 

Important products derived from amino acids include heme, purines, pyrimidines, hormones, neurotransmitters, and biologically active peptides. In addition, many proteins contain amino acids that have been modified for a specific function such as binding calcium or as intermediates that serve to stabilize proteins—generally structural proteins—by subsequent covalent cross-hnk-ing. The amino acid residues in those proteins serve as precursors for these modified residues. Small peptides or peptide-like molecules not synthesized on ribosomes fulfill specific functions in cells. Histamine plays a central role in many allergic reactions. Neurotransmitters derived from amino acids include y-aminobutyrate, 5-hydroxytryptamine (serotonin), dopamine, norepinephrine, and epinephrine. Many drugs used to treat neurologic and psychiatric conditions affect the metabolism of these neurotransmitters. 

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