Benzodiazepine inhibits anxiogenic-like response in cocaine or ethanol withdrawn planarians.

Planarians spend less time in light versus dark environments. We hypothesized that planarians withdrawn from cocaine or ethanol would spend even less time in the light than drug-naive planarians and that a benzodiazepine would inhibit this response. Planarians pretreated in cocaine or ethanol were placed at the midline of a Petri dish containing spring water that was split evenly into dark and light compartments. Planarians withdrawn from cocaine (1, 10, 100 µmol/l) or ethanol (0.01%) spent less time in the light compartment than water controls; however, this withdrawal response to cocaine (100 µmol/l) or ethanol (0.01%) was abolished by clorazepate (0-100 µmol/l). These data suggest that planarians, similar to rodents, show benzodiazepine-sensitive, anxiogenic-like responses during cocaine or alcohol withdrawal.

Craniofacial skeletal pattern: is it really correlated with the degree of adenoid obstruction?

OBJECTIVE: The aim of this study was to compare the cephalometric pattern of children with and without adenoid obstruction.METHODS: The sample comprised 100 children aged between four and 14 years old, both males and females, subjected to cephalometric examination for sagittal and vertical skeletal analysis. The sample also underwent nasofiberendoscopic examination intended to objectively assess the degree of adenoid obstruction.RESULTS: The individuals presented tendencies towards vertical craniofacial growth, convex profile and mandibular retrusion. However, there were no differences between obstructive and non-obstructive patients concerning all cephalometric variables. Correlations between skeletal parameters and the percentage of adenoid obstruction were either low or not significant.CONCLUSIONS: Results suggest that specific craniofacial patterns, such as Class II and hyperdivergency, might not be associated with adenoid hypertrophy.

OBJETIVO: a presente pesquisa teve como objetivo comparar o padrão cefalométrico de crianças com e sem obstrução adenoidiana.MÉTODOS: a amostra consistiu de 100 crianças, com idades entre 4 e 14 anos, de ambos os sexos, submetidas a exames cefalométricos para a avaliação de variáveis cefalométricas horizontais e verticais. A amostra também foi submetida à nasofibroendoscopia, por meio da qual o grau de obstrução adenoidiana foi objetivamente aferido.RESULTADOS: os pacientes avaliados demonstraram tendência ao crescimento vertical acentuado, ao perfil convexo e à retrusão mandibular. No entanto, não houve diferenças entre pacientes portadores e não portadores de obstrução, em relação a todas as variáveis cefalométricas. As correlações estabelecidas entre os parâmetros esqueléticos e os percentuais de hipertrofia foram baixas ou não significativas.CONCLUSÕES: os resultados sugerem que padrões faciais específicos, tais como Classe II e hiperdivergência, parecem não estar associados à hipertrofia adenoideana.

Benzodiazepines increase the reward effects of buprenorphine in a conditioned place preference test in the mouse.

Buprenorphine (BPN) is widely used as a substitution treatment for opioid addiction. Some cases of abuse and misuse, especially associated with various benzodiazepines (BZDs), have been described, and a previous study has shown that BZDs increase the sedative effect of BPN and decrease its anxiogenic properties. To investigate the reward effect that may lead to the abusive combination of BPN and BZD, we studied the influence of different doses of three BZDs extensively used with BPN by drug addicts on conditioned place preference behavior in mice. BPN (0.3, 1, 3 mg/kg) was injected subcutaneously into male mice alone or in combination with a BZD administered intraperitoneally: dipotassium clorazepate (CRZ; 1, 4, 16 mg/kg), diazepam (DAZ; 0.5, 1, 5 mg/kg), or bromazepam (BMZ; 0.5, 1, 3 mg/kg). Amphetamine (8 mg/kg) was used as a reference drug. Reward effects of BPN alone or in combination were measured in a conditioned place preference paradigm using an unbiased procedure. Our results showed that groups treated with BPN associated with different doses of diazepam and clorazepate, but not bromazepam, spent significantly more time in the drug-paired compartment compared to the group treated with BPN alone. Our study shows that joint consumption of diazepam and clorazepate, but not bromazepam, can increase the reward properties of BPN alone in mice. These results could help to explain the use of this type of drug combination in the drug addict population.

Differential behavioral profile induced by the injection of dipotassium chlorazepate within brain areas that project to the nucleus accumbens septi.

BACKGROUND: The effect of the agonism on γ-aminobutyric acid (GABA) receptors was studied within medial prefrontal cortex (mPFC), amygdala (AMY) and ventral hipocampus (VH) in the plus-maze test in male rats bilaterally cannulated. These structures send glutamatergic projections to the nucleus accumbens septi (NAS), in which interaction and integration between these afferent pathways has been described. In a previous study of our group, blockade of glutamatergic transmission within NAS induced an anxiolytic like effect. METHODS: Three rat groups received either saline or dipotassium chlorazepate (1 or 2 µg/1 µl solution) 15 min before testing. Time spent in the open arms (TSOA), time per entry (TPE), extreme arrivals (EA), open and closed arms entries (OAE, CAE) and relationship between open- and closed-arms quotient (OCAQ) were recorded. RESULTS: In the AMY injected group TSOA, OAE and EA were increased by the higher doses of dipotassium chlorazepate (p < 0.01). In the mPFC, TPE was decreased by both doses (p < 0.05). Injection within ventral hippocampus (VH) decreased TSOA, OAE and OCAQ with lower doses (p < 0.05). When the three studied saline groups were compared, TSOA, OAE, EA and OCAQ were enhanced in the VH group when compared to mPFC and AMY (p < 0.001). Insertion of inner canula (p < 0.001, p < 0.01, p < 0.01) and saline injection showed an increasing significant difference (p < 0.001 in all cases) with the action of guide cannula alone within VH in TSOA, OAE and EA. CONCLUSION: We conclude that the injection of dipotassium chlorazepate has a differential effect depending of the brain area, leading to facilitatory and inhibitory effects on anxiety processing.

[Tolerance of prostate biopsy with use of local anesthesia and benzodiazepines: a randomized, prospective study]. / Tolerancia a la biopsia prostática con el uso de anestesia local y benzodiacepinas: estudio prospectivo aleatorizado.

INTRODUCTION: Prostate biopsy is an uncomfortable procedure, and attempts are therefore being constantly made to try and decrease biopsy-related pain. MATERIALS AND METHODS: A randomized, prospective study including 160 procedures was designed. Inclusion criteria were: first biopsy, PSA < 15 ng/mL, and age under 75 years. Patients were randomized into 4 groups. Group A was the control group, while group B received intracapsular anesthesia (8 mL of 2% lidocaine), group C 5 mg of oral clorazepate dipotassium one hour before biopsy, and group D both local anesthesia and clorazepate. Each patient completed a questionnaire including three 10-point visual analog scales for pain immediately after the procedure and 30 minutes later. RESULTS: Mean pain scores were 5.17 (group A), 1.72 (group B), 2.43 (group C), and 0.88 (group D) in the first questionnaire, and 1.71, 0.25, 0.75 and 0.35 respectively in the second questionnaire. Statistically significant differences were found in the ANOVA test. Group comparisons showed the following: 1. A vs B: statistically significant differences in both questionnaires (p = 0.006 and 0.011). 2. A vs C: a significant difference was found in the first questionnaire (0.051), but not in the second (0.012). 3. A vs D: significant differences in both questionnaires (0.001 and 0.010). No statistically significant differences were seen in both questionnaires (0.825 and 0.685) when benzodiazepines where added to local anesthesia (B vs D). CONCLUSION: Use of benzodiazepines as a single method to decrease biopsy-related pain is not warranted.

[Abuse of alcohol and benzodiazepine during substitution therapy in heroin addicts: a review of the literature]. / Abus d'alcool et de benzodiazépines lors des traitements de substitution chez l'héroïnomane : une revue de la littérature.

INTRODUCTION: In spite of its seriousness, dependence on alcohol and benzodiazepines during substitution treatment are poorly documented. Its frequency is nonetheless significant. According to studies, between one and two thirds of patients are affected. This consumption is under verbalized by patients and underestimated by carers. In one study, where the average diazepam doses were from 40 to 45 mg per day, 30% of the patients were taking 70 to 300 mg per day, two thirds having experimented with a fixed dose of 100mg. Benzodiazepines, especially diazepam and flunitrazepam, were studied versus placebo. Thus, 10 to 20mg of diazepam gave rise to euphoria, a sensation of being drugged, sedation and lessening of cognitive performance. The aim of this consumption is to potentiate the euphoria induced by opioids, a "boost" effect during the hour after taking it, or the calming of the outward signs of withdrawal. The most sought after molecules are the most sedative, those with pronounced plasmatic peaks, and the most accessible. LITERATURE FINDINGS: In multidependant subjects, opioid dependence had been earlier in adolescence, with a number of therapeutic failures. They had been faced with repetitive rejection and separation during childhood, medicolegal and social problems. Somatization, depression, anxiety and psychotic disorders are frequent in this subgroup. Heavy drinkers under methadone treatment are highly vulnerable to cocaine. Their behaviour is at risk, with exchange of syringes; their survival rate is 10 years less than that of moderate consumers of alcohol. Most are single, with a previous prison, psychiatric or addictive cursus and they present significant psychological vulnerability. For some authors, benzodiazepines indicate a psychiatric comorbidity. Methadone significantly reduces the consumption of alcohol by nonalcoholic heroin addicts. Although alcohol is an enzymatic inductor of methadone catabolism, with bell-shaped methadone plasma curves over 24 hours, a substitution treatment is recommended. It has a minimum impact on care, in spite of efficiency and retention in therapeutical programs, allowing the subject's inclusion in the framework of a more regular and sustained medical follow-up. Treatment of benzodiazepine dependence by a progressive regression of doses has little efficacy in subjects which cannot control how much medication they are taking. Certain authors have suggested maintenance treatments of clonezepam. The most appropriate therapeutic propositions are: (1) maintenance of therapeutic links though a framework of deliverance from flexible substitution treatment; (2) prevention by cautious prescribing and control of dispensing medication; (3) parallel treatment of psychiatric comorbidities and related personality disorders; (4) individual psychiatric treatment, either institutional or in consistent networks.

[Comparison of premedication regimes. A randomized, controlled trial]. / Prämedikationsregime im Vergleich. Eine prospektive, randomisierte, kontrollierte Studie.

BACKGROUND: The effect of two premedication regimes with different benzodiazepines on anxiety, hemodynamic data, sympatho-adrenal activity, and bispectral index (BIS) was evaluated during the variable time period prior to induction of anesthesia. PATIENTS AND METHODS: This prospective, double-blind study was performed with 50 ASA class I and II patients. Patients were randomized either to group I: evenings 22.00 hours 50 mg chlorazepate dipotassium (CD), mornings 07.00 hours 25 mg CD, placebo 30 min prior to anesthesia (on demand) or group II: evenings 50 mg CD, mornings placebo, 7.5 mg midazolam on demand. RESULTS: In group I the BIS dropped after administration of 25 mg CD and was significantly lower at 08.00, 09.00 and 10.00 hours compared to baseline (mean+/-SD; 90+/-5, 87+/-7 and 87+/-7, respectively vs. 95+/-4; p<0.05), whereas the BIS of group II did not decrease significantly. Both groups did not differ significantly with respect to all variables obtained throughout the study period. CONCLUSION: We conclude that 50 mg CD the evening before surgery prevented an increase of anxiety and sympatho-adrenal activity in both groups and might therefore be sufficient as premedication. Fixed time application of 25 mg CD at 07.00 hours or 7.5 mg midazolam 30 min prior to anesthesia did not further affect these variables preoperatively.

Flumazenil-sensitive dose-related physical dependence in planarians produced by two benzodiazepine and one non-benzodiazepine benzodiazepine-receptor agonists.

Two benzodiazepine (midazolam and clorazepate) and one non-benzodiazepine (zolpidem) benzodiazepine-receptor agonists produced dose-related physical dependence, as evidenced by abstinence-induced decrease in planarian locomotor velocity (pLMV) when drug-exposed planarians were placed into drug-free water, but not when they were placed into drug-containing water (i.e., an abstinence-induced withdrawal, since the effect was only obtained in the removal of drug and not in the continued presence of drug). We have previously shown that the decrease in pLMV is associated with specific and transient withdrawal signs. In the present study, the selective benzodiazepine-receptor antagonist flumazenil significantly antagonized (P<0.05), by co-application, the ability of each agonist to produce the withdrawal. These results: (1) suggest that benzodiazepine-receptor agonists, for two different chemical categories, produce dose-related physical dependence manifested as abstinence-induced withdrawal in this simple and convenient model, and (2) in the absence of cloning or radioligand binding literature, suggest a possible specific interaction site (receptor?) for these compounds in planarians.

Acute and chronic administration of clorazepate modifies the cell surface regulation of mu opioid receptors induced by buprenorphine in specific regions of the rat brain.

The aim of the present study was to investigate the acute and chronic effects of clorazepate (CRZ) alone or in combination with buprenorphine (BPN) on binding of the selective mu opiate tritiated ligand [3H]-DAMGO in the rat brain. Using 0.1 to 5 nM [3H]-DAMGO concentrations and a beta-imager, Bmax (maximal receptor density) and K(D) (the dissociation constant) were directly determined at different regions of interest (ROI) in the brains of rats treated with BPN and/or CRZ administered either once or over 21 consecutive days. Differences in Bmax and K(D) were related to both treatment and location. Acute BPN induced a down-regulation (62% mean decrease in Bmax observed on the whole brain) of mu opiate receptors. CRZ induced a mean 39% decrease in Bmax associated with substantially decreased affinity, particularly after acute administration (136% mean K(D) increase). Addition of CRZ to BPN [mean Bmax decreases of 34% (acute) and 29% (chronic)] induced significantly less down-regulation than did BPN alone, while altering affinity. These changes were maximal in the amygdaloid nucleus. Significant and persistent decreases in Bmax and affinity were also detected in the hippocampus, hypothalamus and thalamus. In the thalamus, an opposite regulation of Bmax was observed that was maximal with the combination. As the regions where changes were greatest have been specifically implicated in memory and socio-emotional functions and/or vegetative and endocrine adaptations, there is reason to suspect that the addition of CRZ to BPN may have clinical consequences. On the one hand, it may have some impact on drug abuse and misuse behaviors towards treatments including heroin substitute and BZD, and on the other, amplify the BPN effect-particularly hedonic or toxic-mainly after sporadic BPN-BZD abuses. These pharmacodynamic findings may explain, at least in part, the well-established preference of patients for the BPN-benzodiazepine combination and the toxicity with which it is associated.

Differences between the tolerance characteristics of two anticonvulsant benzodiazepines in the amygdaloid-kindled rat.

The characteristics of the development of tolerance to the anticonvulsant effects of chronic treatment by dipotassium clorazepate and diazepam using amygdaloid-kindled rats were investigated. Dipotassium clorazepate (5 mg/kg) or diazepam (5 mg/kg) were intraperitoneally administered for 10 consecutive days. Tolerance to the anticonvulsant effect of dipotassium clorazepate developed in seizure stage on day 6, after-discharge duration on day 7 and seizure latency on day 4. In contrast, tolerance to the effects of diazepam developed more rapidly in seizure stage on day 4, after-discharge duration on day 4 and seizure latency on day 3. Thus tolerance to the anticonvulsive effect of dipotassium clorazepate developed relatively slower than that to diazepam. All rats had stage 5 convulsions 24 hr after cessation of the administration of dipotassium clorazepate and diazepam. Concomitant determinations of plasma concentrations of the main metabolite of dipotassium clorazepate and diazepam, desmethyldiazepam, showed no statistical difference during treatment, suggesting that the developed tolerance was not metabolic but functional.

[Optimizing anesthesiologic premedication with reference to biopsychological theories. Exemplified by the effect of dipotassium clorazepate and zolpidem in combination with promethazine]. / Optimierung der anästhesiologischen Prämedikation unter Berücksichtigung biopsychologischer Erklärungsansätze. Aufgezeigt am Beispiel der Wirkung von Dikaliumclorazepat und Zolpidem in Kombination mit Promethazin.

UNLABELLED: The following double-blind randomized placebo-controlled study dealt with three questions: 1. Are differentiated psychometric test systems suitable measuring emotions before anaesthesia? 2. What are the effects of different doses of zolpidem (8.03 mg vs. 16.06 mg) compared with dipotassiumclorazepat (10 mg vs. 20 mg) on emotions in premedication? 3. Is the combination with Promethazin suggestive? METHOD: 320 patients were randomly assigned to different regimes of preanaesthetic medication. As primary premedication they received either zolpidem 8.03 mg or zolpidem 16.06 mg or dipotassium clorazepate 10 mg or dipotassium clorazepate 20 mg or placebo. The secondary premedication was either promethazine 50 mg or placebo. The tablets/dragees were given in the evening before surgery (09.00 p.m.-10.00 p.m.). Every cell of the 5 x 2-factorial design contained 16 men and 16 women. Emotions were measured by a multidimensional rating scale, comprising the aspects elated mood, anxiety, hostility, deactivation, vigilance and introversion. In addition, somatic symptoms and the quality of sleep were measured. Statistics were performed using multivariate analysis of variance. RESULTS: No differing effects of zolpidem and dipotassium clorazepate on preoperative mood were found. There was also no difference compared with placebo. Compared with placebo, promethazin leads to greater deactivation. Specific emotions were not affected. In somatic aspects there was a greater amount of cholinergic effects under promethazine, which was mainly expressed by a higher intensity of a dry mouth and weakness in general. Compared with placebo all of the tested drugs led to a better quality of sleep. CONCLUSIONS: Using multidimensional rating scales and considering emotions as a multifactorial construct, the study shows no different effects of benzodiazepines or benzodiazepin-like drugs on preoperative mood. No differences were also found on comparing these drugs with placebo. However, a better quality of sleep was seen under zolpidem and dipotassium clorazepate compared with placebo. The study shows that a combination with promethazine is recommended, because promethazine has a selective deactivating effect. The study stresses the significance of multidimensional rating scales for the measurement of emotions before anaesthesia.

Safety and effectiveness of an oral premedication regimen before cardiac surgery.

Thirty-five adult cardiac surgical patients received 20 mg dipotassium clorazepate orally the evening before surgery and 2 mg flunitrazepam 60 min before induction of anaesthesia. If anaesthesia was to be induced after 08.30 hours patients received an additional 20 mg dipotassium clorazepate at 06.15 hours. The following measurements were made: peripheral arterial oxygen saturation (Spo2) breathing room air; anxiety by visual analogue scale; degree of sedation; and haemodynamic variables. Mean (Spo2) was 95.9% (SD 1.8%) on the day before surgery and 95.4% (SD 1.5%) on arrival at the operating room. When the operation started after 08.30 hours, mean (Spo2) at 09.00 hours was 96.0% (SD 1.4%). There were no detected episodes of hypoxaemia after premedication. Mean anxiety score decreased significantly from 3.9 (SD 2.6) on the day before surgery to 3.3 (SD 2.1) on arrival at the operating room (patients' score; P < 0.002) and from 4.6 (SD 2.4) to 3.3 (SD 2.0) (anaesthesiologists' score; P < 0.001). Nearly all patients were considered well sedated, which was reflected by normal haemodynamic variables on arrival at the operating room. The combination of clorazepate and flunitrazepam is effective oral premedication for adult cardiac surgery, causing no obvious desaturation even when supplemental oxygen is not given.

[Comparison of the effectiveness of orally administered clorazepate dipotassium and nordiazepam on preoperative anxiety]. / Vergleich der Wirkung von oral appliziertem Dikaliumclorazepat und Nordiazepam auf die präoperative Angst.

Clorazepate dipotassium (Tranxilium) is one of the benzodiazepines which is widely used for oral premedication. After oral administration it is decarboxylated to its active metabolite nordiazepam (desmethyldiazepam). Nordiazepam is also commercially available in the form of drops (Tranxilium N). The aim of the present study was to compare the effect of these drugs on preoperative anxiety. One hundred and eight patients scheduled for orthopaedic surgery (ASA I-II) were studied. Medication was administered at 10 p.m. the evening before surgery (E) and at 7 a.m. on the morning of surgery (M). There were four groups: 1) E no medication; M clorazepate dipotassium; 2) E no medication; M nordiazepam; 3) E clorazepate dipotassium; M clorazepate dipotassium, 4) E clorazepate dipotassium; M nordiazepam. Dosages were: clorazepate dipotassium: body weight < 55 kg: 10 mg; body weight > 55 kg: 20 mg; nordiazepam: 1 gtt/kg; 5 mg = 24 gtt). Anxiety was measured by using the self-evaluating Erlangen anxiety scales, which measure both background and situational anxiety. Background anxiety (EAS-H) was evaluated during the evening before surgery; situational anxiety (EAS-S) was evaluated at the same time and also on the day of surgery before premedication and immediately before surgery. Pulse rate was measured each time the test was administered. There were no differences between the groups in sex, age, weight or the intervals between premedication and anaesthesia induction (p > 0.05). There were no statistically significant differences between the groups with respect to background anxiety. Situational anxiety did not significantly increase or decrease at any of the testing times, nor were there any differences between the groups (p > 0.05). Heart rate did not vary between the groups or with time (p > 0.05). In this group of patients undergoing elective orthopaedic procedures, clorazepate prevented a rise in anxiety in the immediate preoperative period. Since clorazepate is rapidly metabolized to nordiazepam when administered orally it might be predicted that the two drugs have similar properties. This hypothesis is confirmed by the results of the present study. We conclude that orally administered clorazepate dipotassium and nordiazepam have a similar effect on preoperative anxiety.

Potentially toxic serum concentrations of desipramine after discontinuation of valproic acid.

Pharmacological interventions in the treatment of various cognitive, behavioural and neurological problems after brain injury often may involve combinations of medications from various drug classes. This carries the implication of potentially new or previously underreported drug interactions. A case report is presented in which a commonly used anticonvulsant drug, valproic acid, and a commonly used antidepressant, desipramine, interacted in such a manner as to cause potentially toxic serum concentrations of desipramine. This case demonstrates the important point that it is not simply the addition of one drug to another that may cause interaction, but the withdrawal of a particular drug which may then adversely impact the remaining drug regimen.

Effects of a 44-day administration of phenobarbital on disposition of clorazepate in dogs.

The disposition of clorazepate, a benzodiazepine anticonvulsant, was determined in dogs after administration of a single oral dose of clorazepate (2 mg/kg of body weight) and after oral administration of clorazepate (2 mg/kg, q 12 h) concurrently with phenobarbital (5 mg/kg, q 12 h) for 44 consecutive days. Serum concentrations of nordiazepam, the active metabolite of clorazepate, were measured. After a single oral dose of clorazepate, maximal nordiazepam concentrations ranged from 569.6 to 1,387.9 ng/ml (mean, 880.2 +/- 248.9 ng/ml) and were detected 16.8 to 131.4 minutes (mean, 85.2 +/- 36 minutes) after dosing. After administration of phenobarbital for 44 consecutive days, maximal nordiazepam concentrations were significantly (P < 0.01) lower, ranging from 209.6 to 698.5 ng/ml (mean, 399.3 +/- 155.6 ng/ml) at 68.4 to 145.8 minutes (mean, 93 +/- 25.8 minutes) after dosing. Mean area under the curve (AUC) on day 1 (mean, 3.37 +/- 0.598 ng.min/ml) was significantly (P < 0.001) greater than AUC on day 44 (1.66 +/- 0.308 ng.min/ml). Oral clearance was significantly (P < 0.01) greater on day 44 (12.44 +/- 2.55 ml/min/kg), compared with that on day 1 (6.16 +/- 1.35 ml/min/kg). Values for area under the first moment curve, oral volume of distribution, mean residence time, and elimination half-life were not significantly altered by concurrent administration of phenobarbital. Administration of phenobarbital altered the disposition of clorazepate such that the amount of nordiazepam in circulation during each dose interval was significantly reduced. Adequate control of seizures in epileptic dogs, therefore, may require higher dosages of clorazepate when it is coadministered with phenobarbital.

Case study of neuroleptic-induced akathisia: important implications for individuals with mental retardation.

Neuroleptic-induced akathisia is a relatively common side effect of neuroleptic medication, characterized by a subjective sense of restlessness and the inability to sit still. It has been associated with aggression, anxiety, sleep disturbance, and suicide among patients who have mental illness. These side effects are fairly well-researched in the psychiatric literature but rarely addressed in the mental retardation literature. The prevalence, types of akathisia, differential diagnosis, and treatment were reviewed and a relevant case report presented. The importance of the diagnosis and treatment of neuroleptic-induced akathisia in individuals with mental retardation was discussed.

Oral clonidine premedication prevents the rise in intraocular pressure following succinylcholine administration.

The objective of the study was to assess the effects of premedication with clonidine on intraocular pressure (IOP) after the administration of succinylcholine. Fifty elderly patients undergoing ophthalmic surgery were randomly allocated to two study groups. Group 1 patients (n = 25) received clonidine, 300 micrograms p.o. In group 2 (n = 25), the benzodiazepine dipotassium clorazepate was given p.o. at a dose of 0.3 mg.kg-1. Anesthesia was induced with thiopental 3-4 mg.kg-1, alfentanil 10 micrograms.kg-1, atracurium 0.07 mg.kg-1, and succinylcholine 1 mg.kg-1. Nine IOP measurements were taken in each patient starting before premedication and ending 3 min after endotracheal intubation. In both groups, there was a decrease in IOP after induction of anesthesia with thiopental and alfentanil. Succinylcholine administration and endotracheal intubation had no further effect on IOP in the clonidine group. In group 2, succinylcholine caused an increase in IOP when compared with the post induction value. We conclude that clonidine premedication can prevent the increase in IOP following succinylcholine administration.