Effects of clonidine and yohimbine on the pupillary light reflex and carbachol‐evoked sweating in healthy volunteers.

Morley, M. J.; Bradshaw, C. M.; Szabadi, E.

doi:10.1111/j.1365-2125.1991.tb03864.x

Cited by 31 publications

(49 citation statements)

References 8 publications

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“…In the present experiment, a single dose of 0.2 mg clonidine reduced both the subjective and the objective level of alertness in healthy volunteers (see Table 1), in agreement with previous reports (Morley et al, 1991;Kumari et al, 1996;Abduljawad et al, 1997Abduljawad et al, , 2001Phillips et al, 2000d;Hou et al, 2005. Alertness was robustly increased by a single dose of 400 mg modafinil, in contrast to previous reports using a 200-mg single dose where either a small effect (Hou et al, 2005(Hou et al, , 2007 or no effect of modafinil in healthy non-sleep-deprived volunteers was observed.…”

Section: Discussioncontrasting

confidence: 56%

Modulation of the Acoustic Startle Response by the Level of Arousal: Comparison of Clonidine and Modafinil in Healthy Volunteers

Samuels

Hou

Langley

et al. 2007

Neuropsychopharmacol

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A sudden loud sound evokes an electromyographic (EMG) response from the orbicularis oculi muscle in humans together with an auditory evoked potential (AEP) and an increase in skin conductance (SC). Startle responses are inhibited by weak prepulses (prepulse inhibition, (PPI)) and may also be modified by the level of alertness. We compared the sedative drug clonidine and the alerting drug modafinil on sound-evoked EMG, AEP, and SC responses, on the PPI of these responses and on level of arousal and autonomic functions. Sixteen healthy male volunteers participated in four weekly sessions (clonidine 0.2 mg, modafinil 400 mg, their combination, placebo) in a double-blind, cross-over, balanced design. Responses were evoked by sound pulses of 115 and 85 dB (PPI) for 40 ms and recorded conventionally. Level of alertness, autonomic functions (pupil diameter, blood pressure, heart rate, salivation, temperature) and the plasma levels of the hormones prolactin, thyroid-stimulating hormone and growth hormone were also measured. Data were analyzed with analysis of variance with multiple comparisons. Both prepulses and clonidine attenuated all three startle responses and modafinil antagonized clonidine's effects on the EMG and AEP responses. None of the drugs affected PPI. Clonidine showed sedative and sympatholytic effects, and modafinil showed alerting and sympathomimetic effects. In conclusion, startle responses were susceptible not only to PPI but also to the level of arousal. Keywords: acoustic startle response; auditory evoked potential; skin conductance; prepulse inhibition; clonidine; modafinil INTRODUCTIONThe startle response involves rapid involuntary contractions of facial and skeletal musculature in response to a sudden intense stimulus. In the case of the acoustic startle response, this reaction occurs in response to a sudden loud sound and is measurable in humans as an electromyographic (EMG) response from the orbicularis oculi muscle (eyeblink startle response). This response is believed to be mediated via a pathway below the level of the diencephalon consisting of between three and five central synapses, originating from the sensory receptors and terminating on the motor neurons, where the principal relay is the caudal pontine reticular nucleus (Davis et al, 1982; for review, see Yeomans and Frankland, 1996;Koch, 1999). In addition to this muscular response, changes in electroencephalographic (EEG) activity can be observed in response to the auditory stimulus, and these changes are termed auditory evoked potentials (AEP). In particular, the N1/P2 component of the AEP is measurable following the presentation of the acoustic startle stimulus (for examples, see Abduljawad et al, 1999Abduljawad et al, , 2001 Phillips et al, 2000a, b;Graham et al, 2001Graham et al, , 2004Scaife et al, 2005Scaife et al, , 2006. Both the muscular and the AEP responses are fast responses; longer-latency responding to the startle stimulus can be observed in autonomic activity, in particular in sympathetically mediated skin conductance...

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Section: Discussioncontrasting

confidence: 56%

Modulation of the Acoustic Startle Response by the Level of Arousal: Comparison of Clonidine and Modafinil in Healthy Volunteers

Samuels

Hou

Langley

et al. 2007

Neuropsychopharmacol

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“…Moreover, the slopes and intercepts of the fitted regression lines did not differ significantly in the presence of the antidepressants from those observed in the presence of placebo, indicating that the observed reduction in recovery time ( Figure 1, Table 2) is likely to be the reflection of the reduction in reflex response amplitude. It is possible that the reduction in amplitude in the presence of the antidepressants militated against the detection of any effect on the sympathetic input, since previous studies have suggested that a sympathetic contribution to the recovery phase of the light reflex response becomes apparent only at larger response sizes [5,6]. In theory, the range of response amplitudes in the presence of the antidepressants could have been extended to the same level as observed in the presence of placebo by the application of more intense light stimuli.…”

Section: Discussionmentioning

confidence: 99%

“…The computer could be programmed to pass current pulses of predetermined intensity and duration through the diodes and also to determine the time intervals between the applications of successive stimuli. The following twelve light intensities were used: 5.3 x 10-5, 1.5 x 104, 5.0 x 10-4, 1.7 x 10-3, 5.3 x 10-, 1.5 x 10-2, 4.6 x 10-2, 0.13, 0.36, 0.86, 1.86 and 3.5 mW cm-2 (measured 1 cm from the light source). The stimulus duration was 500 ms, and the interval between successive stimuli was 20 s.…”

Section: Apparatusmentioning

confidence: 99%

“…prolong the recovery time [5], and variables that enhance sympathetic activity (e.g. high ambient temperature) shorten the recovery time of the reflex response [6].…”

Section: Introduction Light Reflexmentioning

confidence: 99%

“…The effector organ is a smooth muscle diaphragm, the iris, which receives a dual sympathetic/parasympathetic innervation. Both innervations contribute to the light reflex: while the latency and amplitude of the reflex response are almost exclusively determined by activity in the parasympathetic [1][2][3], the time required for the pupil to redilate to its original size after the cessation of the light stimulus ('recovery time') is significantly influenced by activity in the sympathetic nerve supply to the iris [2, [4][5][6]. Thus it has been shown that drugs that block muscarinic cholinoceptors in the iris (e.g.…”

Section: Introduction Light Reflexmentioning

confidence: 99%

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Effects of reboxetine and desipramine on the kinetics of the pupillary light reflex.

Theofilopoulos

McDade

Szabadi

et al. 1995

Brit J Clinical Pharma

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Reflex responses were evoked by 12 light stimuli (5.3 x 10-5-3.5 mW cm-2; 500 ms), and the kinetic parameters of each response were recorded. 4 The amplitude and 75% recovery time were positively, and latency was negatively correlated with the logarithm of light stimulus intensity. In the presence of the antidepressants the latency was prolonged, the amplitude was reduced and the 75% recovery time was shortened. There was a positive linear relationship between reflex amplitude and recovery time under all three treatment conditions; this relationship was not significantly affected by the antidepressants. 5 The effects of the antidepressants on latency and amplitude are consistent with the blockade of muscarinic cholinoceptors in the iris, whereas the shortening of the recovery time appears to be secondary to the reduction in amplitude.

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A comparison of the effects of single doses of amoxapine and amitriptyline on autonomic functions in healthy volunteers

Bourne

Szabadi

Bradshaw

1993

Eur J Clin Pharmacol

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We have studied the effects of single oral doses of amoxapine (100 mg and 200 mg), amitriptyline (50 mg and 100 mg), and placebo on some autonomic functions in ten healthy volunteers, using a balanced double-blind crossover design. Amitriptyline significantly reduced salivation and it significantly attenuated both miosis evoked by locally applied pilocarpine and sweat secretion evoked by locally applied carbachol. Amoxapine did not significantly alter any of these measures. Neither treatment significantly altered the pupillary light reflex (latency, amplitude, or 75% recovery time). Resting pupil diameter was significantly reduced by the higher dose of amoxapine but was not affected by the other treatments. The higher dose of amoxapine significantly increased supine systolic blood pressure, but did not affect heart rate or diastolic blood pressure; amitriptyline had no effect on any of these cardiovascular measures. These results confirm the antimuscarinic effects of amitriptyline in man, but provide no evidence for antimuscarinic effects of amoxapine.

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Effects of clonidine and yohimbine on the pupillary light reflex and carbachol‐evoked sweating in healthy volunteers.

Cited by 31 publications

References 8 publications

Modulation of the Acoustic Startle Response by the Level of Arousal: Comparison of Clonidine and Modafinil in Healthy Volunteers

Modulation of the Acoustic Startle Response by the Level of Arousal: Comparison of Clonidine and Modafinil in Healthy Volunteers

Effects of reboxetine and desipramine on the kinetics of the pupillary light reflex.

A comparison of the effects of single doses of amoxapine and amitriptyline on autonomic functions in healthy volunteers

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