Tryptamines effects

Kay DC, Martin WR. (1978). LSD and tryptamine effects on sleep/wakefulness and electrocorticogram patterns in intact cats. Psychopharmacology (Berlin). 58(3) 223-28. 

Yohimbine (104), also from the bark of C.johimbe K Schum. and from the roots of R. serpentina (1. ) Benth. has a folk history (unsubstantiated) of use as an aphrodisiac. Its use has been confirmed experimentally as a local anesthetic, with occasional employment for rehef ia angiaa pectoris and arteriosclerosis, but is frequently contraindicated by its undesired renal effects. Yohimbine and some of its derivatives have been reported as hahuciaogenic (70). In addition, its pattern of pharmacological activities ia a variety of animal models is so broad that its general use is avoided. All ten carbon atoms of secologanin (102) as well as the entire skeleton of tryptamine (98, R = H) are clearly seen as iatact portions of this alkaloid. 

Tetrahydroharman, m.p. 179-80°, has been prepared by a number of workers by a modification of this reaction, viz., by the interaction of tryptamine (3-)5-aminoethylindole) with acetaldehyde or paraldehyde and Hahn et al. have obtained a series of derivatives of tetrahydronorharman by the use of other aldehydes and a-ketonic acids under biological conditions of pH and temperature, while Asahina and Osada, by the action of aromatic acid chlorides on the same amine, have prepared a series of amides from which the corresponding substituted dihydronorharmans have been made by effecting ring closure with phosphorus pentoxide in xylene solution. 

Although the exact mechanisms of action of LSD and tryptamine-related compounds are incompletely understood (Freedman 1987), there is convincing evidence relating the psychotomimetic effects of these substances to serotonergic transmission in the brain (Davis 1987 Freedman 1987 McCall 1986 Nichols 2004). An antagonism of 5-HT in the rat brain is sufficient to cause a fourfold decrease in the threshold dose ofLSD (Appel and Freedman 1964). 

The action of 5-HT on brain neuronal systems is complex depending on the neurons involved, it can induce inhibition or excitation. Experiments with iontophoretic application of LSD to neurons have shown that 5-HT-induced excitation is invariably blocked by LSD, whereas LSD mimics inhibition at sites where 5-HT exerts an inhibiting effect (Aghajanian et al. 1987 Martin and Sloane 1986). Tryptamine itself is found in all major regions of... 

These opposing effects of tryptamine and 5-HT are also seen when they are applied directly to cortical neurons by iontophoresis. Tryptamine is predominantly depressant while 5-HT is mainly excitatory. Surprisingly, the 5-HT antagonist metergoline is more effective against tryptamine and the depressant effects. When the medial Raphe nucleus... 

Possibly there is a subclass of 5-HT receptors that would be preferentially activated by tryptamine if its endogenous concentrations were ever adequate. Indeed the term tryptamine receptor as first used by Gaddum to describe the effects of all indole amines may be one to which we should return. 

Commins et al. (1987) have also reported the formation of 5,6-dihydroxy-tryptamine in rat hippocampus after a single, high doses of methamphetamine. They suggested that the formahon of 5,6-dihydroxytryptamine, a known neurotoxie substance, may mediate the neurotoxie effects of methamphetamine toward serotonergic nerve terminals. 

MAOI (Monoamine Oxidase Inhibitors) will intensify and prolong the effects of NN-DMT, however this is never recommended. Foolish combinations of MAOIs and other drugs can lead to serious health problems and even death. The tryptamines are normally metabolized by an MAO in the body. MAO metabolizes serotonin, norepinephrine, and dopamine. By inhibiting this, MAOIs increase levels of those neurotransmitters. Tyramine will not be metabolized and will cause an increase in tyramine levels in blood. 

Further evidence for serotonergic mediation of the effects of hallucinogens was provided by a report on the development of functional supersensitivity in the rat with a chronic denervation of spinal 5-HT neurons. Nygren et al. (138) reported that rats pretreated with intracistemally administered 5,6-dihydroxy-tryptamine (5,6-DHT), a 5-HT neurotoxin, subsequently showed greater hindlimb extensor facilitations to 5-MeODMT or L-tryptophan + nialamide at 1 week versus 1 day following pretreatment. 

Using a standardized method for eliciting flexion (electrical stimulation of the base of the hindpaw) and a quantifiable method of contraction measurement (force transducer attached to the hindpaw), Nozaki et al. (136,137) found that LSD (10 Mg/kg) and tryptamine both increased the flexor reflex in acutely spinalized rats. Both these effects were blocked by pretreatment with the 5-HT antagonist cyproheptadine. A similar LSD effect was reported in spinal cats (118). 

Commissaris, R. L., Lyness, W. H., Moore, K. E., and Rech, R. H. (1981) Central 5-hydroxy-tryptamine and the effects of hallucinogens and phenobarbital on operant responding in rats. Pharmacol Biochem. Behav., 14 595-601. 

In summary, primary amine and monoalkyl derivatives of tryptamine have not yet been demonstrated to produce hallucinogenic effects in man or to consistently produce profound behavioral effects in animals. Admittedly, relatively few compounds have been examined, and few studies have been conducted. Nevertheless, present evidence suggests that these derivatives, by virtue of their inability to penetrate the blood-brain barrier and/or their rapid metabolism, may not be able to achieve adequate brain levels to elicit effects. In some cases, these factors may lead to masking of potential central effects by peripheral actions of the compounds or their metabolites. 

Trulson, M. E., and Jacobs, B. L. (1979) Effects of 5-methoxy-N.N-dimethyl-tryptamine on behavior and raphe unit activity in freely-moving cats. Eur. J. Pharmacol., 54 43-50. 

Evoked potential studies showed that LSD facilitated a PSR this effect was blocked by cyproheptadine (18). The 5-HT agonist quipazine augmented a PSR this effect was blocked by cinanserin but (curiously) not by metergoline (80). Finally, tryptamine (183) and L-tryptophan (19) have been reported to increase PSRs in a cyproheptadine-reversible manner. 

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