Neuroactive

V. Chan-Palay and S. Palay, eds.. Coexistence of Neuroactive Substances in Neurons, John Wiley Sons, Inc., New York, 1984. 

AHopregnanolone and similar A-ring-reduced pregnanes potentiate GABA effects at these receptors. These steroids mimic the effects of the benzodiazepines, changing chloride ion conductance and producing sedative and hypnotic behavioral effects (276,277). Neuroactive steroids can be therapeutically useful as anticonvulsants, anxiolytics, or anesthetics (qv) (see also Hypnotics, sedatives, anticonvulsants, and anxiolytics). 

H-Asp-Met-His-Asp-Phe-Phe-Val-Gly-Leu-Met-NH2. Physalaemin, eledoisin, kassinin, SCYl, and SCYll are nonmammalian tachykinins. Two larger peptides have been identified, neuropeptide K (328) and neuropeptide y (329), both of which interact with tachykinin receptors (Table 19). The NKA sequence is contained within the carboxy-terrninal sequences of both neuropeptide K and neuropeptide y. Like other neuroactive peptides, tachykinin peptide precursors are synthesized ribosomaHy and transported to nerve terminals where further processing occurs. 

A moderate neuroactivity of 1,3-dioxacyclanes 200 and 202 has been revealed (78KFZ61). 

Glycine receptor function is modulated by alcohols and anesthetics [4]. Amino acid residue al(S267) is critical for alcohol potentiation, as mutation to small residues (Gly, Ala) enhance, and mutation to large residues (His, Cys, Tyr) diminish the ethanol effect. Glycine recqrtor modulation by Zn2+ involves structural determinants located within the large N-terminal domain. Additional glycinergic modulators include neuroactive steroids and the anthelmintic, ivermectin, which activates glycine receptors by a novel, strychnine-insensitive mechanism. 

Neurosteroids are neuroactive steroids, which are synthesized in the brain. Neurosteroids can bind to and modulate the activity of y-aminobuty tie acidA(GABA A) receptors. 

Methyl-l,2,3,9-tetrahydro-4H-carbazol-4-one, the key building block of the neuroactive compound alosetron, was easily obtained from 3-[(2-halophenyl)(methyl)amino]cyclohex-2-en-l-one by pyrrole ring formation via Heck reaction under microwave irradiation [94], While the iodo substrate gave an excellent yield in only 30 min at 100 °C the corresponding bromo derivative converted only poorly under the same reaction conditions (Scheme 88). 

Tissue plasminogen activators Human growth hormone Neuroactive peptides Regulatory peptides Lymphokines Human serum albumin Gamma globulin Antihemophilic factors Monoclonal antibodies... 

Neurosteroids differ from nearly all the other transmitters and mediators in that they are lipid-soluble and can easily cross the blood-brain barrier. Thus it is necessary to distinguish those steroids that are produced in the brain from those that find their way there from the circulation after being released from the adrenal cortex or gonads. There are many natural and synthetic steroids that have some effect on neuronal function and can be considered neuroactive but few are actually produced in the brain to act on neurons, i.e. the true neurosteroids. 

With so many different neurosteroids with differing and even opposing neuronal effects, much will depend on their relative concentrations at any time and any evaluation of their function must take this into consideration. Hopefully the synthesis and use of appropriate antagonists will throw more light on the physiological role of steroids in the CNS and facilitate the development and clinical use of new neuroactive steroids (see Gasior et al. 1999). 

Gasior, M, Carter, RB and Witkin, JM (1999) Neuroactive steroids potential therapeutic use in neurological and psychiatric disorders. Trends Pharmacol. Sci. 20 107-112. 

Rupprecht R and Holsboer F (1999) Neuroactive steroids mechanisms of action and neuropsychopharmacological perspectives. Trends Neurosci. 22 410-416. 

Snake venoms, neuroactive, 21 (1984) 63 Sodium cromoglycate analogues, 21 (1984) 1... 

The organ also contains neuroactive compounds as constituents of the vasomotor and neuro-glandular tissues (Zancanaro et al., 1997). These include the amine transmitters Nor-adrenalin and Serotonin (5-HT), whose presence is presumably related to the non-olfactory innervations. Local stimulation effects [Figs. 5.2 and 5.5(a)] can alter the biogenic amine levels in the VNO of female mice, as a result of exposure to male conspecific urine, and consequent arousal of the suction-pump [c.f. Fig. 5.7(a)]. 

An additional and widespread neuroactive (transmitter-like) compound is nitric oxide (NO). This gaseous secretion is a product of the action of the enzyme NO-synthase on arginine. It is implicated in at least two roles within the non-sensory tissues of the organ, and at particular synapses in the AOB. One nitric oxidergic effect is initiated by the nerve fibres supplying the smooth muscle component of the vasomotor tissues. The other effect is the expected action of NO on the output... 

Fig. 31. Example of neuroactive indole alkaloids from plants. Note the similitude of chemical structure of harmine, harmaline, and serotonin.

The family Myristicaceae has about 16 genera and 380 species of tropical lowland rainforest trees that are easily recognizable in field collection because of their bloodlike sap, conical crown, and nutmeg-like fruits. A very interesting feature of Myristi-caeae species are their ability to elaborate series of neuroactive indole alkaloids, because it produces neuroactive indole alkaloids, which might hold potential for the treatment of anxiety, mood disorders, and other psychological disturbances. 

The histaminergic neurons have several well-developed primary and secondary dendrites that overlap with each other. Furthermore, long dendrites from histaminergic neurons located close to the mammillary recess or to the basal surface of the mammillary body appear to penetrate into the ependymal layer and make contact with cerebrospinal fluid. Thus, it is likely that neuroactive substances such as cytokines, present in the cerebrospinal fluid, may influence the discharge activity of TMN neurons (Wada et al., 1991). Unlike the dopaminergic neurons, which are known to release dopamine from their dendrites, there is no evidence that these histaminergic dendrites store and/or release HA. 

Tohyama, M. Takatsuji, K. (1998). Atlas of Neuroactive Substances and Their Receptors in the Rat. Oxford Oxford University Press. 

Porcu, P., Sogliano, C., Cinus, M., Purdy, R.H., Biggio, G., Concas, A. Nicotine induced changes in cerebrocortical neuroactive steroids and plasma corticosterone concentrations in the rat. Pharmacol. Biochem. Behav. 74 683, 2003. 

Llerena A et al. Relationship between personality and debrisoquine hydroxyla-tion capacity. Suggestion of an endogenous neuroactive substrate or product of the cytochrome P4502D6. Acta Psych Scand 1993 87(l) 23-28. 

While steroids generated in the brain have been referred to as neurosteroids , another useful term is neuroactive steroids to refer to all steroids that affect brain function via any mechanism and irrespective of site of formation. The term neuroactive steroid also has been used to describe neuroactive steroid drugs. 

Estradiol. The first neuroactive steroid receptor type to be recognized was that for estradiol [3]. In vivo uptake of [3H] estradiol, and binding to cell nuclei isolated from hypothalamus, pituitary and other brain regions, revealed steroid specificity closely resembling that of the uterus, where steroid receptors were first discovered [3]. Cytosolic estrogen receptors isolated from pituitary and brain tissue closely resemble those found in uterus and mammary tissue. A hallmark of the estrogen receptor is its existence... 

Mihalek, R. M., Banerjee, P. K., Korpi, E. R., and Quinlan, J. J. (1999) Attenuated sensitivity to neuroactive steroids in y-aminobutyrate type A receptor 8 subunit knockout mice. Proc. Natl. Acad. Sci. USA 96,12905-12910. 

---