Dr. David E. Nichols, an American pharmacologist and medicinal chemist, is renowned for his significant contributions to the study of serotonin and dopamine receptors. Born on December 23, 1944, in Covington, Kentucky, Nichols has had a distinguished career in the field of psychoactive drugs since 1969. As a graduate student, he developed a patented method for synthesizing optical isomers of hallucinogenic amphetamines. His work has spanned various aspects of medicinal chemistry and pharmacology, with a focus on the structure-activity relationship (SAR) of hallucinogens, research into MDMA neurotoxicity, and MDMA analogues​​.
Nichols's contributions include the synthesis and reporting of various psychedelic compounds and the development of novel analogues of MDA and MDMA. He has also been a leader in dopamine research, developing several notable dopamine receptor ligands, including compounds researched for treating Parkinson's disease and schizophrenia​​.
Turning to serotonin receptors, these are a group of G protein-coupled receptors and ligand-gated ion channels found in the central and peripheral nervous systems. They mediate both excitatory and inhibitory neurotransmission and are activated by the neurotransmitter serotonin. These receptors modulate the release of several neurotransmitters and hormones, influencing a variety of biological and neurological processes, including mood, appetite, cognition, and sleep​​​​.
There are 7 families of serotonin receptors, classified as 5-HT 1 to 5-HT 7, with a total of 14 known types. The 5-HT 1 and 5-HT 5 families are Gi/Go-protein coupled and tend to decrease cellular levels of cAMP, providing an inhibitory response. The 5-HT 2 family is Gq/G11-protein coupled, increasing cellular levels of IP3 and DAG, and generally results in an excitatory response. The 5-HT 3 receptor is a ligand-gated ion channel, while the 5-HT 4, 5-HT 6, and 5-HT 7 families are Gs-protein coupled, increasing cellular levels of cAMP and generally providing an excitatory response​​​​.
Regarding 5-HTP and tryptophan, both are amino acids and precursors to serotonin. 5-HTP is a direct precursor of serotonin and an intermediate in the synthesis of melatonin, while tryptophan is a direct precursor of 5-HTP and is involved in the synthesis of other biochemicals. 5-HTP is considered a better supplement for increasing serotonin levels in the central nervous system because it does not compete with other amino acids to cross the blood-brain barrier, and it directly bypasses the rate-limiting step in the synthesis of serotonin​​​​.
Tryptophan, predominantly found in protein-rich foods, is limited in its ability to increase blood levels of the amino acid due to competition for transport across the blood-brain barrier. It is used as a supplement for its role in serotonin synthesis, and its uptake into the brain is improved with carbohydrate intake​​. 5-HTP, on the other hand, is a naturally occurring amino acid produced from L-tryptophan, with no direct dietary sources. It is used in supplements for its ability to increase serotonin levels in the brain, as well as a sleep aid, antidepressant, and appetite suppressant​​​​.
However, caution should be exercised when using these supplements, as concurrent use of 5-HTP and tryptophan can lead to serotonin toxicity, with symptoms ranging from mild gastrointestinal issues to severe conditions like serotonin syndrome and cardiac fibrosis​​.
