Biphasic effect

There are similarities between the biological actions of inhalants and those of alcohol and barbiturates (Bowen et al. 1996b). For example, acute administration of inhalants affects motor coordination (Moser and Balster 1981) and induces anxiolysis, whereas chronic administration is associated with physical dependence and withdrawal (Bowen et al. 1996a Evans and Balster 1991, 1993). In addition, some inhalant drugs have anticonvulsant properties (Wood et al. 1984). Like other CNS-depressant agents, inhalants have biphasic effects on spontaneous locomotor activity in rodents, with increased activity seen at lower doses and diminished locomotion seen at higher doses (Cause et al. 1985 Kjellstrand et al. 1985). 

ANDERSON J J B, AMBROSE w w and GARNER s c (1998) Biphasic effects of genistein on bone tissue in the ovariectomized, lactating rat model. Proc Soc Exp Biol Med 217, 345-50. 

Amphetamine may engender a dose-dependent biphasic effect on aggressive behavior in experimental situations, both with human and animal subjects, as, for example, in subjects that have habituated to an aggression-provoking stimulus. Most often, however, amphetamines disrupt social, sexual, maternal, and aggressive behavior patterns in a dose-dependent manner ... 

The biphasic effect of divalent cations such as calcium on APTT is well recognized. Thus, whereas the addition of 0.025 M calcium chloride to citrated plasma has no effect on the APTT result, both higher and lower calcium chloride concentrations such as 0.065 or 0.004 M can artifactually elevate the APTT result (100). 

Monti J., Hawkins M., Jantos H., DAngelo L., Fernandez M. (1988). Biphasic effects of dopamine D-2 receptor agonists on sleep and wakefulness in the rat. 

Paul How did that differ from what we have been told about here, with Ca2+ having a biphasic effect independent ofInsP3 Or did I just miss something ... 

Zhu, B.-Z. and Chevion, M. (2000). Copper-mediated toxicity of 2,4,5-trichlor-ophenol biphasic effect of the copper(I)-specific chelator neocuproine, Arch. Biochem. Biophys., 380, 267-273. 

Ye L, Martin TA, Parr C, Harrison GM, Mansel RE, and Jiang WG [2003] Biphasic effects of 17-/3-estradiol on expression of occludin and transendothelial resistance and paracellular permeability in human vascular endothelial cells. J Cell Physiol 196 362-369... 

It is interesting that modifying solution conditions by adding different concentrations of ethanol can produce a biphasic effect on melting transition temperatures of lipid-like systems (e.g., acyl chains of hydrocarbons). For example, low concentrations of ethanol reduce the Tm of phosphatidylcholine bilayers, whereas higher concentrations increase the Tm of the same system.122 This effect has been shown to depend upon acyl chain length and can be explained by the... 

Intracellular messengers A biphasic effect of ginkgo extract is seen on cAMP phosphodiesterase under in vitro and ex vivo conditions (Saponara and Bosisio 1998 Macovschi et al. 1987). Whereas low concentrations (0.25-4.0 mg/L) activate the enzyme, higher concentrations (5-250 mg/L), dose-dependently inhibit it. However, tolerance develops to this effect because it is undetectable after daily administration for 4 days. Thus, ginkgo may initially produce effects by inhibiting enzymatic breakdown of cAMP. This mechanism is similar to the stimulant caffeine, but it is not likely to explain any long-term effects of ginkgo because it disappears after chronic daily treatment. The responsible constituent for this effect has not been identified. 

Physioiogicai There is an extensive literature that deals with the effects ginseng on CNS function, but effects are also seen in neuroendocrine function, carbohydrate and lipid metabolism, the immune system, and cardiovascular function (Gillis 1997). Ginsenosides induce a decrease in heart rate and have biphasic effects on blood pressure, with decreases preceded by a slight increase (Kaku et al. 1975). Ginsenoside Rgl had the most potent effects on blood pressure. Little or no effect is observed on respiration. 

However, another controlled study in Alzheimer s disease patients found only marginal improvements in picture recognition and ratings of word-finding ability (Tariot et al. 1988). No benefits were seen in semantic or episodic memory. Biphasic effects were found on psychomotor activation, with improvements at lower doses and impairments at higher doses. 

Paradoxically, catnip fed to mice had stimulant effects, with increased rearing, locomotion, and stereotypical behavior, increased susceptibility to chemically induced (picrotoxin and strychnine) seizures, and decreased sleeping time after barbiturate administration (Massoco et al. 1995). The LD50 for nepetalactone in mice was reported to be quite high at 1300 mg/kg (Harney et al. 1978). In chicks, an a cohol extract of catnip had biphasic effects, where low to moderate doses (25-1800 mg/kg) produced sedative effects, while higher doses (>2 g/kg) had less sedative and perhaps stimulant effects (Sherry and Hunter 1979). Humans have reported sedative effects of catnip, and one accidental ingestion by a young child reportedly produced sedative effects (Osterhoudt et al. 1997). 

Pedata F, Pepeu G, Spignoli G. (1984). Biphasic effect of methyixanthines on acetylcholine release from electrically-stimulated brain slices. Br J Pharmacol. 83(1) 69-73. 

Striatum and lateral septum. Interestingly, in contrast to our findings in the hippocampus, CRH has biphasic effects in these brain structures. Low doses of CRH (0.1 and 0.3 pg) were found to decrease extracellular levels of 5-HT. Higher doses of CRH (1.0 and 3.0 pg) have, however, no effect or increase 5-HT levels in the striatum and lateral septum (Price et al. 1998 Price and Lucki 2001). The biphasic effects on levels of 5-HT in these brain regions may be related to the dose-dependent effects of CRH on the firing rate of DRN 5-HT neurones as described above. Interestingly, local injection of CRH in the DRN results in a decrease in extracellular 5-HT in the striatum and septum (Price and Lucki 2001). 

Ehrensing RH, Kastin AJ Dose-related biphasic effect of prolyl-leucylglycinamide (MlF-1) in depression. Am J Psychiatry 135 562-566, 1978 Ehrlich BE, Diamond JM, Ery V, et al Lithium s inhibition of erythrocyte cation countertransport involves a slow process in the erythrocyte. J Membr Biol 75 233-240, 1983... 

Shibata, A., Yamamoto, M., Yamashita, T., Chiou, J.S., Kamaya, H., Ueda, I. (1992). Biphasic effects of alcohols on the phase transition of poly(ot-lysine) between Ot-helix and P-sheet conformations. Biochemistry, 31, 5728-5733. 

ERK1/2 phosphorylation by involving G /o proteins, PKC and tyrosine kinase-dependent and -independent pathways. It has been found that Cl-IB-MECA produced a biphasic effect on cAMP accumulation with a stimulatory action starting at a concentration of 3 nM. This activity was triggered through PLC/PKC and not via direct Gs coupling (Germack and Dickenson 2004, 2005). 

Palitzsch, K.D., Horales, R.E., Kronauge, J.F., Szabo, S., 1989. Biphasic effect of histamine on hemorrhagic mucosal lesions is related to vascular permeability studies with histamine, Hi-, H2- and H3-agonists and bradykinin. Gastroenterology 96, (Suppl.) A381. 

Lu C., Chan S. L., Haughey N., Lee W. T., and Mattson M. P. (2001). Selective and biphasic effect of the membrane lipid peroxidation product 4-hydroxy-2,3-nonenal on V-methyl-D-aspartate channels. J. Neurochem. 78 577-589. 

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