Serotonin analog

FIGURE 15.52 Serotonin analogs resulting from a functional reversal. ... 

LSD (Fig. 10-9), as the D-isomer, psilocin, and dimethyltryptamine are all potent hallucinogens containing the indole nucleus. They may therefore be viewed as serotonin analogs. They are 5-HT antagonists. 

Tierney AJ, Mangiamele LA (2001) Effects of serotonin and serotonin analogs on posture and agonistic behavior in crayfish. J Comp Physiol A 187 757-767... 

HTia (serotonin) receptor binding Various serotonin analogs 327/1993... 

Methylenedioxymethamphetamine (MDMA ecstasy) is a synthetic analog of amphetamine that produces hallucinations, an elevation in mood, and a feeling of emotional closeness . This latter property has led to Ecstasy being referred to as the hug drag . The unique properties of Ecstasy as compared to the parent compound amphetamine are believed to be due to the more selective effects of Ecstasy in promoting transporter-mediated release of serotonin. The use of Ecstasy has become a part of the culture associated with rave style dance parties. 

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 This latter compound proved to lack MDMA-like activity (Shulgin, unpublished).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). 

Fuller, R.W. Wong, D.T. Snoddy, H.D. and Bymaster, F.P. Comparison of the effects of 6-chloro-2-aminotetralin and of Org 6582. a related chloramphetamine analog, on brain serotonin metabolism in rats. 

Johnson, M.P. Hoffman, A.J. and Nichols, D.E. Effects of the enantiomers of MDA, MDMA and related analogs on [ H] serotonin and [ Hjdopamine release from superfused rat brain slices. Eur J Pharmacol 132 269-276, 1986. 

G.K.W. Effects of certain hallucinogenie amphetamine analogs on the release of [ H]serotonin from rat brain synaptosomes. J Med Chem 25 530-535, 1982. 

FIGURE 2. Competition curves of R(-)-DOI for [ HJketanserin binding to 5-HT2 serotonin receptors in rat frontal cortex membranes in the presence and absence of the guanine nucleotide analog Gpp(NH)p... 

A fourth approach to evaluating the intactness of dopamine and/or serotonin neurons in human subjects who have taken one of the amphetamine analogs might be to use a probe for labeling a constituent of those neurons in position emission tomography scanning studies. A label for the serotonin or dopamine uptake carrier, or a label for tryptophan hydroxylase or tyrosine... 

Adding the second alpha-methyl to MDA gives a compound that apparently is only weakly active in man (199). Again, the 3,4-methylenedioxy substitution seems anomalous. This may also be due to an indirect effect, such as release of endogenous neurotransmitter from nerve terminals. However, neither this a,a-dimethylated MDA analog nor a,a-dimethyl-4-methoxy-/3-phenethylamine had any ability to induce the release of 3H-serotonin from rat whole brain synaptosomes (160). 

This method, although described for indoles, probably also worlds with 5-OH-tryptamine (serotonin), and 5-OH-DMT (bufotenin) with compounds of the latter type, orally active psilocybin analogs will be obtained in one step. Dissolve 5 g 5-OH-indole (or analog) in 25 ml ethanol. Add 5.5 g 33% aqueous dimethylamine (or other amine, e.g., piperidine) and add slowly dropwise with stirring 3.5 g 38% aqueous formaldehyde. Two minutes after the end of the addition shake with water and CHCI3 dry and evaporate in vacuum the CHClj phase to get 5 g oily 4-dimethyl-aminomethyl-5-OH-indole (1) (can chromatograph on 100 g alumina and elute with ethyl acetate). It has been claimed that this method does not work. 

Intraperitoneal injections of eugenol and its natural analogs produce unconsciousness in rats, accompanied by slow-wave activity on the EEC (Sell and Carlini 1976). Cerebral levels of dopamine, norepinephrine, and serotonin are not apparently altered. 

Watts VJ, Lawler CP, Fox DR, Neve KA, Nichols DE, Mailman RB. (1995). LSD and structural analogs pharmacological evaluation at D1 dopamine receptors. Psychopharmacology (Berlin). 118(4) 401-9. Wei D, Maisonneuve IM, Kuehne ME, Glick SD. (1998). Acute iboga alkaloid effects on extracellular serotonin (5-HT) levels in nucleus accumbens and striatum in rats. Brain Res. 800(2) 260-68. 

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