The modification of the pupillary light reflex by chlorpromazine, diazepam, and pentobarbital

doi:10.1016/0006-8993(73)90595-7

Brain Research

Volume 50, Issue 1, 14 February 1973, Pages 77-86

https://doi.org/10.1016/0006-8993(73)90595-7 Get rights and content

Abstract

Single light flashes or electrical stimulation of the optic nerve evoke a bi- or triphasic potential in the short ciliary nerves. The central conduction and transmission time (from the optic nerve to the emergence of the preganglionic autonomic oculomotor fibers) is estimated to be about 12 msec. After prior conditioning stimuli, evoked responses to subsequent test shocks are inhibited when the interval is between 15 and 30 msec. Recovery takes 120 msec or longer. This inhibitory period is prolonged by pentobarbital. CPZ, which constricts the pupil in man, enhances optically evoked ciliary potentials, whereas diazepam and pentobarbital decrease them. The CPZ effect is interpreted as a diminution of inhibitory influences on the pupilloconstrictor outflow.

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Cited by (12)

Acute Ataxia in Children: A Review of the Differential Diagnosis and Evaluation in the Emergency Department
2016, Pediatric Neurology
Citation Excerpt :
Clinical features include lethargy advancing to coma, with respiratory depression as an important feature to be aware of.72 Although the sedative effects of many substances can cause pupillary constriction,73 benzodiazepines have been shown to not affect the pupil size in the same way opiates might.74 Amnesia and diplopia are two other features that have been described in the dental literature.75
Acute ataxia in a pediatric patient poses a diagnostic dilemma for any physician. While the most common etiologies are benign, occasional individuals require urgent intervention. Children with stroke, toxic ingestion, infection, and neuro-inflammatory disorders frequently exhibit ataxia as an essential—if not the only—presenting feature. The available retrospective research utilize inconsistent definitions of acute ataxia, precluding the ability to pool data from these studies. No prospective data exist that report on patients presenting to the emergency department with ataxia. This review examines the reported causes of ataxia and attempts to group them into distinct categories: post-infectious and inflammatory central and peripheral phenomena, toxic ingestion, neurovascular, infectious and miscellaneous. From there, we synthesize the existing literature to understand which aspects of the history, physical exam, and ancillary testing might aid in narrowing the differential diagnosis. MRI is superior to CT in detecting inflammatory or vascular insults in the posterior fossa, though CT may be necessary in emergent situations. Lumbar puncture may be deferred until after admission in most instances, with suspicion for meningitis being the major exception. There is insufficient evidence to guide laboratory evaluation of serum, testing should be ordered based on clinical judgement—recommended studies include metabolic profiles and screening labs for metabolic disorders (lactate and ammonia). All patients should be reflexively screened for toxic ingestions.
Mydriasis model in rats as a simple system to evaluate a2-Adrenergic activity of the imidazol(in)e compounds
2013, Pharmacological Reports
Citation Excerpt :
Since Yu and Koss [65] proved that imidazoline receptors are not functionally involved in rat clonidine mydriasis, that in vivo experimental model could be widely applied in preclinical research to characterize α2-adrenoceptor activity of drugs. It was suggested by Warwick in 1954 [62], and confirmed by Silito and Zbrożyna [55] in 1970 that the tonic parasympathetic preganglionic cell bodies that innervate the iris are located in the Edinger-Westphal nucleus and antero-median nuclei of the oculomotor complex [55, 62]. Axons emerge in the third cranial nerve and synapse in the ciliary ganglion.
Imidazol(in)e compounds show the diversity of pharmacological effects including mydriasis, hypotension, sedation, bradycardia and hypothermia. At first it was postulated that these effects are mediated via α₂-adrenoceptors exclusively. Clonidine is well known as a model agent to produce pupillary dilation in rats. However, it became obvious later that clonidine-like imidazol(in)e adrenoceptor agonists which produced mydriasis in rats, exhibit also a high affinity for imidazoline I₁-receptors. That short report attempts to review the present status of studies to confirm that the mydriasis model in rats can be a selective system to evaluate the α₂-adrenergic activity of potential pharmacologically active compounds of imidazol(in)e structure.
Relationship between abnormal pupillary reactivity and the outcome of a psychotropic drug overdose
2010, American Journal of Emergency Medicine
Citation Excerpt :
They may also reduce the pupillary light reflex [12]. In a cat study, an intravenous injection of high-dose diazepam (1 mg/kg) depressed the optic tract evoked potential in the short ciliary nerves, thus resulting in a reduction of the light reflex [13]. Accordingly, deep sedation induced by an overdose of a variety of drug may result in abnormal pupil reactivity in this study.
The association between abnormal pupil reactivity (abnormal) and the outcome among patients with psychotropic drug overdose (OD) was retrospectively investigated.
The study included patients that had experienced an OD between January and December 2007. The subjects were divided into 2 groups, namely, abnormal and normal groups.
There were 12 subjects in the abnormal and 74 subjects in the normal group. Glasgow Coma Scale in the abnormal was significantly smaller that that in the normal group. An average quantity of ingested tranquilizer per subject in the abnormal was significantly larger that those in the normal group. However, the duration of admission and survival rates between the two groups were not significantly different.
The patients that experienced an OD, who demonstrated abnormal pupil reactivity, tended to have ingested larger amounts of drugs while also demonstrating severe unconsciousness. However, the patients with abnormal pupil reactivity had a favorable outcome.
Lateralization of pupillary light reflex parameters
2005, Clinical Neurophysiology
The aim of this study was to determine differing reactions of the left and right eyes with regard to pupillary light reflex (PLR) parameters.
All together 90 healthy subjects were included. In the first test series, 34 subjects were investigated on both eyes (left eye was tested first, three tests per day and one reliability test). In the second test series, 32 subjects were studied while changing the beginning side. In the last test series, 29 subjects were investigated 12 times each within 1 h (beginning side changed, without spoken advice). Infrared pupillometry was used to study pupil diameter, latency time, relative amplitude, contraction/dilation velocity, and pupil redilation time.
The study demonstrated significant differences of PLR parameters between both eyes. In contrast to the pupil diameter of the left eye the papasympathetically-dominated right eye was not influenced by vocal instructions or by changing the beginning side.
PLR parameters might indicate functional lateralization of autonomic function in the central nervous system. High sensitivity of the procedure (arousal due to spoken advice, time of day) is advantageous for various psychophysiological investigations.
Differences between both eyes might point towards cortical lateralization of central autonomic function.
Pupillary dilation as an index of central nervous system α<inf>2</inf>-adrenoceptor activation
1986, Journal of Pharmacological Methods
In recent years there has been increasing evidence that some antihypertensive drugs like clonidine and α-methyldopa (after conversion in the brain to α-methylnorepinephrine) may decrease sympathetic tone by stimulating central nervous system (CNS) α₂-adrenoceptors. These same drugs also produce pupillary dilation in cats and rats. In this review, evidence is presented supporting the hypothesis that clonidinelike drugs act either directly or indirectly on CNS postsynaptic α₂-adrenoceptors to cause pupillary dilation by reduction of parasympathetic neural tone to the iris. It is further suggested that the underlying physiologic mechanism for this mydriatic action is activation of an ascending pathway that provides tonic inhibitory input by releasing norepinephrine on neurons in the Edinger-Westphal complex. Yohimbine-sensitive pupillary dilation in these species may provide a simple and effective model for quantitatively accessing CNS α₂-adrenoceptor activity.
CNS adrenergic inhibition of parasympathetic oculomotor tone
1984, Journal of the Autonomic Nervous System
Inhibition of parasympathetic neural tone to the iris was produced by electrical stimulation of the afferent sciatic nerve, medullary reticular formation, and posterior hypothalamus in anesthetized cats in which only the parasympathetic nerves to the eye were intact. Stimulation of all 3 sites of activation produced a graded pupillary dilation and reduction of tonic nerve activity in the short ciliary nerves. Intravenous administration of the α-2-adrenoceptor antagonist, yohimbine hydrochloride, (0.03–1.0 mg/kg) produced a dose-dependent antagonism of the mydriasis elicited by activation of the ascending (sciatic nerve and medullary) mechanisms but did not block the pupillary dilation evoked by stimulation of the system descending from the hypothalamus. This differential action of yohimbine was confirmed directly by means of nerve recordings taken from the parasympathetic nerve to the eye. Depletion of CNS monoamines with reserpine and α-m-p-tyrosine reduced the norepinephrine concentration of the medulla and midbrain by 95% and 97%, respectively. In these depleted preparations, stimulation of the hypothalamus still produced the characteristic mydriasis and inhibition of parasympathetic tonic activity whereas activation of ascending mechanisms (sciatic or medullary) were no longer effective in producing these effects. Taken together, these results suggest that ascending parasympatho-inhibition is mediated by a monoamine (probably norepinephrine) and that inhibition descending from the hypothalamus is mediated by a non-monoaminergic mechanism.

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The modification of the pupillary light reflex by chlorpromazine, diazepam, and pentobarbital

Abstract

Electroenceph. clin. Neurophysiol.

Vision Res.

Brain Research

Brain Research

Brazilin-toluidine O and hematoxylin-Darrow red methods for brain and spinal cord

Stain Technol.

A pharmacological analysis of the action of reserpine on the central autonomic nervous system

J. Pharmacol. exp. Ther.

Les commandes re´ticulaires du syste`me autonome et en particulier de l'innervation sympathique et parasympathique de la pupille

Arch. ital. Biol.

Photic reflex and pretectal region

Arch. ital. Biol.