Serotonin metabolites

Separation methods, multichromato-graphic la 56 Serine la 246,356 lb 132 Serotonin la 70,76,239,240,262,355, 380 lb 37-39,231,243,348 Serotonin metabolites lb 327 Serum lipids la 89 Serum proteins la 74 Sesquiterpene derivatives lb 239,446 Sesquiterpene esters lb 239 Sesquiterpene glucosides la 327 Sesquiterpene lactones lb 448 Sevin lb 387-389 Si 50 000, specific surface area la 91 Silica gel, caffeine-impregnated la 85 -, surface modified la 3 Silica gel 60, specific surface area la 91... 

QUESTION Is there a decrease in serotonin metabolites, and does it show any relationship to age, cumulative dose, and so forth Did you see anything there You have that one person who had 42 grams. Was he any more or any less affected ... 

There are several ways in which possible neurotoxic effects might be studied. First, measurement of cerebrospinal fluid concentrations of dopamine or serotonin metabolites would be a straightforward way of assessing neurotoxicity. There are pitfalls in this approach (as outlined by Dr. Ricaurte (this volume), such as the facts that lumbar cerebrospinal fluid might reflect spinal cord neurochemistry more than it reflected brain neurochemistry, and drugs like /r-chloroamphetamine affect serotonin neurons in spinal cord less than they do those in brain (Sanders-Bush... 

Also, harmala alkaloids create effects on monoamine turnover. Postnatal rats administered harmaline (shortly before birth) have elevations in brain levels of the norepinephrine metabolite 3-methoxy-4-hydroxy-phenylglycol (MHPG), but decreases in the dopamine and serotonin metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindole acetic acid (5-HIAA) (Okonmah et al. 

Stuart JN, Zhang X, Jakubowski JA, Romanova EV, Sweedler JV. 2003. Serotonin catabolism depends upon location of release characterization of sulfated and gamma-glutamy-lated serotonin metabolites in Aplysia californica. J Neuro-chem 84 1358. 

In essentially all species of animals, including humans, serotonin is important in aggression (Kravitz, 2000). Relationships between CSF concentrations of a serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA), and human aggression were described in As-berg et al. s landmark study (1976), which showed a bimodal distribution among depressed patients. A meta-analysis of 27 studies, involving 1202 psychiatric patients, showed an association between attempted suicide and low levels of CSF 5-HIAA (Lester, 1995). 

Lithium has numerous pharmacologic effects. It is able to cross through sodium channels, competing with monovalent and divalent cations in cell membranes (AHFS, 2000). Animal studies have shown that lithium at a serum level of 0.66 + — 0.08 mEq/L can increase the amphetamine-induced release of serotonin (5-hydroxytryptamine [5-HT]) and the concentrations of a serotonin metabolite (e.g., 5-hydroxyindoleacetic acid [5-HIAA]) in the perifornical hypothalamus (PFH) of rats before and after chronic lithium chloride administration (Baptista et ah, 1990), a mechanism possibly involved in lithium s antidepressant effect. The precise neurobiological mechanisms through which lithium reduces acute mania and protects against recurrence of illness remain uncertain (Lenox and Hahn,... 

Neurons guard against accumulating too much serotonin with the use of enzymes such as monoamine oxidase (MAO). This enzyme catalyzes a reaction converting serotonin to a different molecule. Some of these serotonin metabolites—compounds derived from serotonin—are excreted by the body, marking the end of the road for these molecules. 

Argentiero V, Tavolato B Dopamine (DA) and serotonin metabolite levels in the cerebrospinal fluid (CSF) in Alzheimer s presenile dementia under basic conditions and after stimulation with cerebral cortex phospholipids. J Neurol 224 53-58, 1980... 

An association between impulsive aggression, suicidal behavior, or both with decreased CSF levels of the serotonin metabolite 5-HIAA... 

Studies of depressed patients have sometimes shown an alteration in monoamine function. For example, some studies have found evidence of alteration in serotonin receptor numbers (5-HT1A and 5-HT2c) or norepinephrine (k2) receptors in depressed and suicidal patients, but these findings have not been consistent. A reduction in the primary serotonin metabolite 5-hydroxyindoleacetic acid in the cerebrospinal fluid is associated with violent and impulsive behavior, including violent suicide attempts. However, this finding is not specific to major depression and is associated more generally with violent and impulsive behavior. 

The hypothesis that SSRIs work in OCD by a serotonergic mechanism is also supported by studies showing a strong positive correlation between improvement in obsessive-compulsive symptoms during clomipramine treatment and drug-induced decreases in cerebrospinal fluid (CSF) levels of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) and platelet serotonin concentrations. Thus, peripheral markers of 5HT function link the symptomatic improvement in OCD symptoms produced by SSRIs to changes in 5HT function. However, these markers do not consistently highlight a 5HT abnormality in untreated patients with OCD,... 

TCDD was investigated. No changes were found in epinephrine and dopamine in the hypothalamus or in dopamine and its metabolites in the striatum. However, tryptophan (a precursor of serotonin) levels in plasma and brain were increased and this was paralleled by increases in brain serotonin and 5-hydroxyindolacetic acid (the major serotonin metabolite) (Rozman et al. 1991). Based on the results of these experiments, Rozman et al. (1991) proposed that decreased PEPCK activity decreases gluconeogenesis and leads to increased plasma concentrations of glycogenic amino acids, such as tryptophan. Increased tryptophan leads to increase in serotonin release in the brain and to appetite... 

As scientists improved their techniques for detecting low levels of amines, they began to measure the amine concentrations in postmortem human brains. Several researchers measured levels of serotonin and norepinephrine in the brains of people who had committed suicide as a result of depression and compared the levels to individuals of the same age who had been killed in accidents. The suicides brains had lower levels of serotonin. Subsequent studies also revealed that certain depressed patients had lower levels of serotonin metabolites in their cerebrospinal fluid. These findings accelerated the effort to develop drugs that would be effective on serotonergic neurons. 

C. Anticholinergic Hallucinogens (Clinical Effects) -Neubauer et al.9t claim that antagonism to Ditran may require both adrenolytic and cholinomimetic activities. Bauer d FlUgel93 were able to inhibit the psychotomimetic effects of Bayer 1443 and Ditran by the prior administration dihydro-ergotamine. Increased urinary excretion of catecholamine and serotonin metabolites after the administration of N-methyl-3-pyrrolidyl phenylcyclopentylglycolate was demonstrated by Bente et al. 9 ... 

When monkeys have low serotonin levels, they become aggressive. This response is thought to be a model for violence against oneself or family members, possibly related to a failure to counteract epinephrine effects. High aggressiveness in monkeys was correlated with low levels of metabolic products of serotonin in spinal fluid. In humans, low levels of serotonin metabolites in spinal fluid also correlate with the severity of physical aggression. 

In 1976, Asperg and others found reduced levels of the serotonin metabolite 5-HlAA in the cerebrospinal fluid of depressed patients who had made suicide attempts (Arch Gen Psychiatry 1976 33 1193-7). Brown and others also found a relationship between aggression, history of suicidal behavior, and 5-HIAA in cerebrospinal fluid (Psychiatry Res 1979 1 131-9.29). 

In addition to the reagents for detection which are quoted in Table 88, many others have been mentioned in the literature [89, 90, 104] for urine metabolites [78] for serotonine metabolites [14] for hydroxyindoles and -tryptophans [35] with comprehensive data for hydroxyskatoles [19] for the methyl esters of indole-carboxylic acids [i2, 23, 63] for glucobrassicin. 2,4-Dinitrophenylhydrazine (Rgt. No. 82) is suitable for the often feebly reactive indole-aldehydes. 

When large amounts of tryptamine were administered to animals, the serotonin contents of tissues were not increa.sed. Administration of potent inhibitors of monoamine oxidase (MAO) along with tryptamine to prevent its destruction was also without effect. Tryptamine administration did not result in an increased excretion of the serotonin metabolite, 5HIAA. On the other hand, administration of comparable amounts of either tryptophan or 5HTP does increase tissue levels of serotonin and urinary excretion of 5HIAA... 

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