Supersensitivity

Supersensitivity refers to the increased responsiveness of a patient to a drug, resulting either from denervation or administration of a drug (a receptor antagonist) for a prolonged period. For example, the blocking of dopamine receptors by chlorpromazine may cause supersensitivity by upregulating dopamine receptors. 

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Superplasticiy Superplasticizers Super Radiometal Supersaturation Superseed Supersensitization... 

Another common loss process results from electron—hole recombination. In this process, the photoexcited electron in the LUMO falls back into the HOMO rather than transferring into the conduction band. This inefficiency can be mitigated by using supersensitizing molecules which donate an electron to the HOMO of the excited sensitizing dye, thereby precluding electron—hole recombination. In optimally sensitized commercial products, dyes... 

Dyes, polymethine used for dyes having at least one electron donor and one electron acceptor group linked by methine groups or aza analogues aUopolar cyanine, dye bases, complex cyanine, hemicyanine, merocyanine, oxonol, streptocyanine, and styryl. Supersensitization has been reported for these types—18 cites for cyanines, 3 for merocyanine, and 6 for all other polymethine types. 

Fig. 6. Effect of added supersensitizers on a J-aggregated spectral sensitizing dye, l,l -dieth5i-2,2 -quinocyariine chloride [2402-42-8] (1), for which...

Rochais F, Vilardaga JP, Nikolaev VO et al (2007) Realtime optical recording of Pi-adrenergic receptor activation reveals supersensitivity of the Arg389 variant to carvedi-lol. J Clin Invest 117229-235... 

Figure 7.7 Dopamine-induced rotation in the rat in which one (left) nigrostriatal dopamine pathway from the substantia nigra (SN) to the caudate putamen (CP) has been lesioned by a prior injection (14 days) of 6-hydroxydopamine. Amphetamine, an indirectly acting amine, releases DA and so can only act on the right side. Since the animal moves away from the dominating active side it induces ipsilateral rotation (i.e. towards the lesioned side). By contrast, the development of postS5maptic supersensitivity to DA on the lesioned side ensures that apomorphine, a directly acting agonist, is actually more active on that side and so the animal turns away from it (contralateral rotation)...

The ability of the striatum to apparently function normally until it has lost much of its DA can be ascribed in part to denervation supersensitivity, the degeneration of the DA input resulting in an increase in postsynaptic DA receptors and partly to the remaining neurons producing more DA. This is supported by measurements in humans which show that the HVA DA ratio, a measure of DA turnover, is much greater in Parkinsonism patients and by microdialysis in rats with 6-OHDA lesions of the nigrostriatal tract, when the reduction in perfusate (released) DA is very much less than that of neuronal (stored) DA. 

It is equally well known that if a neuron dies, or is destroyed, then any other neuron, which had been innervated by it, gradually becomes supersensitive to the NT it released. In the case of degenerating pyramidal cells this would be glutamate, the excitatory NT. Not surprisingly, undercutting the cortex in animals to produce a deafferentation of some of its neurons not only renders them more likely to show epileptic-like discharges but neurons in hippocampal slices from kindled rats and human focal cortex show supersensitivity to the excitatory amino acids. Such supersensitivity could make some neurons so easily activated that they become epileptic . 

The injection of 6-OHDA into the rat nucleus accumbens produces the expected proliferation of DA receptors and resulting supersensitivity so that doses of apomorphine lower than normal produce a significant attenuation of PPI. This is not seen after the production of supersensitivity by toxin lesions of the substantia nigra and prefrontal cortex. The effects of amphetamine were also mainly modified by accumbens lesions. Thus as DA agonists primarily augment the positive symptoms such findings link these with the accumbens. 

QUESTION I find the technique of challenging the animals with various typic agents quite intriguing for assessment after prolonged exposure to MDMA or amphetamine. How long do those changes last I saw in your slide something on the order of 2 weeks or a few days after the MDMA treatment. If you would come back a few months later, would that supersensitivity still exist ... 

QUESTION What is your view of the role of the supersensitive autoreceptor after 7 days Can you precipitate or replicate a psyehosis ... 

COMMENT/QUESTION I was not relating it to psyehosis either. I am trying to put it in a functional context. Have you speeulated about the role of the supersensitive autoreceptor at that point You eould speculate early on that the subsensitivity autoreceptor favors the potentiation of the behavioral effect. But what might happen when it becomes supersensitive ... 

COMMENT I would favor the view that lethargy and fatigue of postamphetamine withdrawal during the withdrawal phase would be consistent with the shutting off of the dopamine neuron. Still, it is hard to imagine how that would be. First, the amphetamine-induced release is not regulated by the autoreceptor. And, as you say, if it would be impulse related, however weak, it would be regulated. But we do know that after a period of amphetamine intoxication, an individual is supersensitive behaviorally. 

If that is a valid concept, could that have anything to say about the consequence of this supersensitization having behaviorally inhibitory effects ... 

QUESTION If anything was preventing a reward system from being operative, you would, perhaps, tend to see this inhibitory effeet behaviorally. With supersensitization, do you have this kind of a eonsequenee to beat the reward system not being activated ... 

FIG. 11 General mechanism for the heterogeneous photoreduction of a species Q located in the organic phase by the water-soluble sensitizer S. The electron-transfer step is in competition with the decay of the excited state, while a second competition involved the separation of the geminate ion-pair and back electron transfer. The latter process can be further affected by the presence of a redox couple able to regenerate the initial ground of the dye. This process is commonly referred to as supersensitization. (Reprinted with permission from Ref. 166. Copyright 1999 American Chemical Society.)... 

A more quantitative description of the photocurrent responses, taking into account the contributions from back electron transfer and RuQi attenuation, was achieved by IMPS measurements [83]. Considering the mechanism in Fig. 11, excluding the supersensitization step, and the equivalent circuit in Fig. 18, the frequency-dependent photocurrent for a perturbation as in Eq. (42) is given by... 

Cory-Slechta DA, Pokora MJ, Widzowski DV. 1992. Postnatal lead exposure induces supersensitivity to the stimulus properties of a D2-D3 agonist. Brain Res 598 162-172. 

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