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Slower than dipivalyl epinephrine.8 The latter is a phenolic ester and is therefore expected to be more reactive than the aliphatic timolol esters. Collectively, these prodrugs were somewhat more susceptible to hydrolysis in plasma than in ocular tissue homogenates. The O-butyryl prodrug was most susceptible to hydrolysis in the iris-ciliary body homogenate, followed by homogenates of the conjunctiva, corneal stroma, and corneal epithelium. Figure 2 shows the total amount of timolol, ie, prodrug plus timolol formed, permeated across isolated corneas, and Figure 3 shows the percent of each prodrug in hydrolyzed form over the time course of corneal permeation. At 10 min, over 30% of each prodrug was in its hydrolyzed form, and by 120 min all but the Opivalyl prodrug were totally hydrolyzed. Overall, the relative rates of timolol formation from the various prodrugs during corneal permeation, as shown in Figure 3, were consistent with the in vitro incubation results shown in Figure 1. From the plots in Figure 2, the apparent corneal permeability coefficient and corneal transport lag time of timolol and its prodrugs were determined. These parameters are summarized in Table 1 along with the n-octanol pH 7.4 buffer distribution coefficients * of timolol and its prodrugs. Except.
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Referenz 607a Neurologie, 11. Auflage ; Magistris MR, Rsler KM, Truffert A, Myers JP. Transcranial stimulation excites virtually all motor neurones supplying the target muscle. A demonstration and a method improving the study of motor evoked potentials. Brain 121: 437-450, 1998. Department of Clinical Neurology, Geneva University Hospital, Switzerland. Transcranial stimulation has become an established method in the evaluation of corticospinal tract function. Clinical studies mainly address slowing of conduction through measurement of increased central conduction time CCT ; and 'failures' of conduction through observation of marked reductions in the size of the motor evoked potential MEP ; . While CCT is of great interest in detecting subclinical slowing of conduction, the method discloses only gross failures of conduction, since the size of the MEP varies markedly between normal subjects and from one stimulus to another, leading to a broad range of normal values. Furthermore, transcranial stimulation does not appear to achieve depolarization of all spinal motor neurons leading to the target muscles, since in most normal subjects MEPs are smaller in amplitude than the responses evoked by peripheral nerve stimulation. We have developed a triple stimulation technique TST ; which, through two collisions, links central to peripheral conduction and suppresses desynchronization of MEPs. This technique shows that transcranial stimulation does achieve depolarization of all, or nearly all, spinal motor neurons supplying the target muscle in healthy subjects. Our data thus demonstrate that the amplitudes of MEPs are i ; smaller than those of peripheral responses, mostly due to phase cancellation of the action potentials caused by the desynchronization occurring within the corticospinal tract or at spinal cell level and ii ; variable between normal subjects and from one stimulus to another, mostly due to variability of this desynchronization. This technique provides new insights into normal corticospinal tract conduction. It will improve detection and quantification of central motor conduction failures.
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