CNS Levels

Ammo adds probably act as neurotransmitters at a majonty of all synapses in the CNS (Bloom and Iversen, 1971 Krnjevic, 1974). In addition to their role as putative neurotransmitters, these compounds occupy central positions in the general metabolism Qohnson, 1972) It is difficult, if not impossible, to differentiate the amino acid pools related to the metabolic function from the amino acid pools related to the neurotransmitter function. Because of their multiplicity of roles, it is not surprising that the amino acids are widely distributed throughout the CNS m fairly high concentrations (Table 3) 

Microwave Fixation and Brain Amino Acid Levels 

It has been known for many years that GABA levels in the brain rise rapidly after death (Baxter, 1972 Lovell et al., 1963 Shaw and Heine, 1965, Minard and Mushahwar, 1966, Shank and Aprison 1971). Levels of other amino acids are modified postmortem, but not to the same extent as GABA (Perry et al., 1981). Decapitation into liquid nitrogen prevents the postmortem rise in GABA, how- 

Concentrations of Ammo Acids m Vanous Rat Brain Areas 

Brain area GABA, nmol/mg protein Glu, nmol/mg protein Asp, nmol/mg protein Gly, nmol/mg protein Gin, nmol/mg protein 

---

NK2r antagonists. At the CNS level, the efficacy of NK2r antagonists in depression and anxiety is currently being tested. 

Diazepam Being extremely lipophilic, diazepam penetrates quickly into the CNS, but can rapidly redistribute into body fat and muscle. This results in a faster decline in CNS levels and early recurrence of seizures. It is dosed at 5 to 10 mg (or 0.15 mg/kg) and infused no faster than 5 mg/minute. Repeated doses can be given every 5 minutes until seizure activity stops or toxicities are seen (e.g., respiratory depression). Diazepam can also be administered as a rectal suppository, making it possible for non-medical personnel to provide rapid therapy for seizures that develop at home or in public areas.11 The adult dose is 10 mg given rectally and this dose may be repeated once if necessary. Diazepam is erratically absorbed via the intramuscular route therefore, IM administration is not recommended. 

Figure 4a. Typical size distribution of 21 Po, full line BOM results (both screen sets), dashed line EML results, for no growth regime. CN levels below 70 per cm , no SO2 added, humidity 2-5% or 75-90% made no difference. The difference in width is probably due to better resolution for series than for parallel method. Error bars are standard deviations for the measurements.

Figure 4b. Typical size distribution of 218Po, full line BOM, dashed line EML, for growth regime. CN level was in general around 4 X 105 per cm , humidity 3-5%, SO2 introduced concentration 10-20 ppm. The presence of a peak at size. 075y to. lly is not fully understood and may be an artifact of the deconvolution program. Error bars are standard deviations for the measurements.

Figure 4a shows the results for CN levels at 70 cm 3 and below. As pointed out earlier (Holub, 1984), there are no attached radon daughters because the attachment rate is negligible compared to 218Po half life. There is no observable growth and the clusters are very close to the oxide of 218Po. All sets agree reasonably well. Error bars are from repeated measurements. 

All dead within 16 min maximum blood CN levels postmortem were 2.1 mg/kg FW in the low-dose group and 4.2 in the high-dose group... 

Advanced signs of acute poisoning death probable within 30 min. Maximum CN levels, in mg/kg FW, were 1.5 in blood and 0.6 in liver... 

Direct evidence is also available from functional studies that LSD can act as a serotonin antagonist. Anderson (9) has reviewed experiments on spinal reflexes conducted in acute spinal cats in which stimulation of the dorsal roots elicits monosynaptic, polysynaptic, and dorsal root reflexes. Increases in CNS levels of serotonin increased the size of the monosynaptic reflex and decreased the size of the polysynaptic and dorsal root reflexes. The increase in magnitude of the monosynaptic reflex induced by serotonin was blocked by a variety of classic serotonin antagonist drugs in addition, it was blocked by the systemic administration of LSD. Decreases in the other two types of spinal reflexes were unaffected by LSD and the serotonin antagonists. 

The photocyanation of 2-nitrothiophene in KCN solution in water (see page 241) shows not only a normal increase of with increasing [CN ] but also the quantum yield of its consumption equals that of the formation of 2-cyanothiophene. With 2-nitrofuran under similar conditions the 4> value for formation of 2-cyanofuran again increases in the usueiI way with increase of [CN ], levelling off at a limiting value of 0-51 at [CN ] O l m. However, the quantum yield of disappearance of the nitrofuran is 0 51, independent of the cyanide concentration. Evidently, there is a second photoreaction (with water) that complements the cyanation. Indeed 7-butenoIide could be found as a product of irradiation of 2-nitrofuran in water. 

Uses Endogenous depression Action TCA T synaptic CNS levels of serotonin /or norepinephrine Dose Adults. 25 mg PO tid-qid >150 mg/d not OK Elderly. 10-25 mg hs Peds. 6-7 y 10 mg/d 8-11 y 10-20 mg/d >11 y 25-35 mg/d, 4- w/ hepatic insuff Caution [D, +/-] NAG, CV Dz Contra TCA allergy, use w/ MAOI Disp Caps, soln SE Anticholinergic (blurred vision, retention, xerostomia) Interactions T Effects W/ antihistamines, CNS depressants, cimetidine, fluoxetine, OCP, phenothiazine, quinidine, EtOH T effects OF anticoagulants T risk of HTN W/clonidine, levodopa, sympathomimetics T effects W/barbiturates, carbamazepine, rifampin EMS Concurrent use w/ MAOIs have resulted in HTN,... 

VPA s mechanism of action is unclear but its anticonvulsant efficacy may be related to the ability to increase CNS levels of GABA (Table 10-2). Due to its rapid absorption, blood levels peak in 1 to 4 hours after oral administration, and the half-life ranges from 6 to 16 hours. It is metabolized primarily through the liver and is eliminated in the urine. VPA is highly protein-bound and usually does not saturate binding sites at serum levels below 45 to 50 pg/mL. Thus, this level would be the expected minimal threshold for its psychotropic effects. 

Let us first consider the case of Y/D 1. This means that at certain values of the compound nucleus excitation energy, individual levels of the compound nucleus can be excited (i.e., when the excitation energy exactly equals the energy of a given CN level). When this happens, there will be a sharp rise, or resonance, in the reaction cross section akin to the absorption of infrared radiation by sodium chloride when the radiation frequency equals the natural crystal oscillation frequency. In this case, the formula for the cross section (the Breit-Wigner single-lev el formula) for the reaction a + A —> C b + B is... 

Q-wave present in lead Deviation of 4 mm in T-wave inversion in II, Acidosis, CN level of Sanchez et al. (2001)... 

Widely distributed into body fluids. Cladribine IV only rapid plasma renally cleared. Adequate CNS levels may... 

Butyl ether has the ability to dissolve lipids. As a result, it may cause irritation and pain upon contact with eyes and nose mucosa. It also causes dermal irritation and dermatitis upon contact with the skin. Damage caused by butyl ether appears to be scattered loss of epithelial cells due to dissolution of phospholipid cell membranes. At the CNS level, butyl ether, like other volatile organic solvents, depresses the CNS by dissolving in the cell lipid membrane and disrupting the lipid matrix. These effects are known as membrane fluidization. At the molecular level, membrane fluidization disrupts solute gradient homeostasis that is essential for cell function. 

Cyanide is metabolized by the ubiquitous enzyme rhodanase to thiocyanate (SCN"), drawing on the body s sulfur-donor pool for substrate to convert CN" to SCN". Thiocyanate is relatively inert and is cleared by the kidney. The conversion of CN" to SCN" occurs slowly relative to the pharmacological action of CN", so measurement of SCN" is of use in monitoring clearance but not very useful in assessing acute CN" exposure. In an acute exposure, the patient experiences symptoms of toxicity with high blood CN" levels, but the serum SCN" level remains low until 12 to 24 hours later. 

The higher narcotic potency in vivo of the S(+)-isomer of hexobarbital was shown to be related to higher central nervous system (CNS) levels than for the R(-) form, this seems to be due to a better crossing of the blood-brain barrier In a distribution study of (+) and... 

---