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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Brimonidine is a relatively selective alpha-2 adrenoceptor agonist that is being developed for the treatment of glaucoma. Because brimonidine is chemically related to clonidine and has affinity for the nonadrenergic imidazoline receptor, its ocular effects may be unrelated to alpha-2 receptor activation. The objective of this study was to determine the pharmacology of the intraocular pressure (IOP) response to brimonidine in rabbits and monkeys and the side effects (miosis, cardiovascular depression) in monkeys. Conscious albino rabbits and cynomolgus monkeys were pretreated topically with the following receptor antagonists: rauwolscine (alpha-2), idazoxan (alpha-2, imidazoline), SKF 105854 (vascular postjunctional alpha-2), and prazosin (alpha-1). Intraocular pressure, pupil size, or blood pressure/heart rate was monitored noninvasively for 6 hours following dosing. Binding experiments were performed using [3H]brimonidine in membrane preparations from rabbit iris/ciliary body and from monkey cerebral cortex and brain stem. In rabbits, the ocular hypotensive response to brimonidine was unilateral and was inhibited by rauwolscine > idazoxan >> SKF 105854 = prazosin; this ranked order of potency correlated with displacement of [3H]brimonidine in the rabbit iris/ciliary body. In monkeys, brimonidine decreased IOP bilaterally and suppressed cardiovascular function suggesting a CNS site of action. Intraocular pressure and cardiovascular responses to brimonidine were inhibited by idazoxan >> rauwolscine > SKF 105854 = prazosin; a similar profile was obtained for displacement of [3H]brimonidine in monkey brain tissue. Both rauwolscine and idazoxan inhibited the miotic response to brimonidine in monkeys. Taken together, these results indicate that brimonidine stimulates an ocular alpha-2 adrenoceptor to decrease IOP in the rabbit and a CNS imidazoline receptor to decrease IOP, blood pressure, and heart rate in the cynomolgus monkey. The miotic response in the monkey is mediated by an alpha-2 adrenoceptor. The alpha-1 and vascular postjunctional alpha-2 adrenoceptors do not appear to play a role in mediating these responses.
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PMID:Adrenergic and imidazoline receptor-mediated responses to UK-14,304-18 (brimonidine) in rabbits and monkeys. A species difference. 767 89

1. Vomiting and restlessness following ENT and eye surgery are undesirable, and may be related to the emetic and analgesic effects of any analgesic given to augment anaesthesia during surgery. 2. To rationalise the choice of analgesic for routine ENT surgery we examined the intraoperative, recovery and postoperative effects following the administration of either buprenorphine (3.0 to 4.5 micrograms kg-1), diclofenac (1 mg kg-1), fentanyl (1.5 to 2.0 micrograms kg-1), morphine (0.1 to 0.15 mg kg-1), nalbuphine (0.1 to 0.15 mg kg-1), pethidine (1.0 to 1.5 mg kg-1) or saline (as control) given with the induction of anaesthesia in 374 patients. A standardised anaesthetic technique with controlled ventilation using 0.6-0.8% isoflurane in nitrous oxide and oxygen was employed. The study population constituted 7 similar groups of patients. 3. Intraoperatively, their effects on heart rate and blood pressure, airway pressure and intraocular pressure, were similar. This implies, most surprisingly, that neither their analgesic nor their histamine releasing effects were clinically evident during surgery. By prolonging the time to extubation at the end of anaesthesia, only buprenorphine, fentanyl, morphine and pethidine provided evidence of intraoperative respiratory depression. 4. Postoperatively, buprenorphine was associated with severe respiratory depression, prolonged somnolence, profound analgesia and the highest emesis rate. Diclofenac exhibited no sedative, analgesic, analgesic sparing, emetic or antipyretic effects. Fentanyl provided no sedative or analgesic effects, but was mildly emetic. Morphine provided poor sedation and analgesia, delayed the requirement for re-medication and was highly emetic. Nalbuphine and pethidine produced sedation with analgesia during recovery, a prolonged time to re-medication and a mild emetic effect. None provided evidence, from analysis of postoperative re-medication times and analgesic consumption, of any pre-emptive analgesic effect. 5. We conclude that nalbuphine (mean dose 0.13 mg kg-1) and pethidine (mean dose 1.35 mg kg-1), given individually as a single i.v. bolus during induction of anaesthesia, are the most efficacious analgesics for routine in-patient ENT surgery.
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PMID:Analgesics and ENT surgery. A clinical comparison of the intraoperative, recovery and postoperative effects of buprenorphine, diclofenac, fentanyl, morphine, nalbuphine, pethidine and placebo given intravenously with induction of anaesthesia. 788 92

The present study was undertaken to determine the effects of direct administration of the selective alpha 2-adrenoceptor stimulant, B-HT 933, on choroidal blood flow, intraocular pressure and pupil size in anesthetized cats. Anterior segment choroidal blood flow was measured using laser-Doppler flowmetry. B-HT 933 administered by intra-arterial, topical and intracameral routes produced a significant depression of ocular blood flow which was largely abolished by pretreatment with rauwolscine. B-HT 933 did not lower IOP in any of these preparations. The largest doses of B-HT 933 caused a modest mydriasis when given intracamerally. However, this pupillary dilation was not blocked by rauwolscine. These results demonstrate that alpha 2-adrenoceptor activation can produce pronounced depression of anterior segment choroidal blood flow but does not cause a concomitant lowering of IOP or mydriasis in anesthetized cats.
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PMID:Ocular effects of alpha 2-adrenoceptor activation in anesthetized cats. 791

A specific and sensitive gas chromatographic-high-resolution mass spectrometric method for the determination of 5-(3-tert.-butylamino-2-hydroxy)propoxy-3,4-dihydrocarbostyril (carteolol), which is a beta-blocker giving depression of intraocular pressure, was developed to elucidate the pharmacokinetics of its ophthalmic application. Carteolol has been determined by high-performance liquid chromatography but with less satisfactory sensitivity. Carteolol was derivatized with pentafluorobenzoyl (PFB) amide followed by dimethylethylsilyl (DMES) ether, resulting in a high negative-ion current. The PFB-DMES derivative of carteolol was determined by the gas chromatography-negative-ion chemical ionization mass spectrometry (GC-NICI-MS) using selected-ion monitoring at low and high mass spectrometric resolution. the detection limit was less than 100 fg when the fragment ion was monitored at m/z 552.2067 in the NICI mode using methane as a reagent gas. The quantification limit of carteolol in human plasma with this method was less than 30 pg/ml. The proposed GC-MS method is considered to have sufficient specificity and sensitivity to study the pharmacokinetics of carteolol used as an ophthalmic solution.
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PMID:Determination of the beta-blocker carteolol in human plasma by a sensitive gas chromatographic-negative-ion chemical ionization high-resolution mass spectrometric method. 861 64

This study was performed to examine some ocular actions of an opioid agonist. Experiments were performed to evaluate the effects of a delta opioid agonist, DPDPE ([D-pen2, D-pen5]enkephalin (where pen = penicillamine)), on: 1) intraocular pressure (IOP) in rabbits; 2) cAMP accumulation in rabbit iris ciliary bodies (ICBs). Unilateral, topical administration of DPDPE caused bilateral depression of IOP. Intravitreal injection of DPDPE caused a greater IOP decrease than intravitreal injection of NaH2PO4 (vehicle). Topical administration of naloxone partially inhibited the effect of DPDPE on IOP in normal rabbits. In other experiments, DPDPE suppressed both basal and isoproterenol (ISO)-stimulated cAMP accumulation in ICBs. The presence of naltrindole (NTI), a delta receptor antagonist, did not prevent the suppression of cAMP levels by DPDPE. The conclusions drawn from the findings suggest that the lowering of IOP by DPDPE is mediated, in part, by actions at postjunctional (ciliary body) sites and may involve an atypical opioid receptor.
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PMID:Ocular action of an opioid peptide, DPDPE. 877 29

The purpose of the study was to compare the retinal sensitivity of pigmented and albino rabbits to ischemia/reperfusion-induced electroretinogram (ERG) alterations and optic nerve morphological changes. High intraocular pressure (HIOP) was induced by applying a suction-cup on the eye and a depression with an ophthalmodynamometer. HIOP was maintained for lengths of time (30-75 min). Flash ERGs were recorded in dark-adapted animals for ischemia and 2 h reperfusion periods. Two weeks later, histological examination of the retinas and optic nerves was done. Albino rabbits submitted to 45 min HIOP failed to recover b-wave ERG amplitude after 2 h reperfusion, whereas pigmented animals presented a total ERG recovery even if ischemia was maintained as long as 75 min. Intravenous treatment of albino animals with Lazaroid U74389G led to significant ERG recovery at reperfusion. Histological studies show that pigmented rabbit optic nerves suffered less damage than the albino ones. These results emphasize the role of the pigmentary status of the animals in the retinal sensitivity to ischemia. Neuroprotection afforded by the antioxidant U74389G suggests that ocular pigments could also protect the retinal functional integrity through a free radical scavenging activity.
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PMID:Differential effect of ischemia/reperfusion on pigmented and albino rabbit retina. 887 40

Acetazolamide (Diamox) is a carbonic anhydrase inhibitor commonly used in patients with glaucoma in order to reduce intraocular pressure. Acetazolamide (AZ) is mostly excreted in the urine, therefore, the blood levels of AZ often tend to increase in patients with chronic renal failure. We experienced a case of chronic renal failure in a patient suffering from acute hemorrhagic gastritis associated with AZ intoxication. A 66-year-old female with chronic renal failure was referred to our hospital because of drowsiness and an acute deterioration of renal function. She had been treated with AZ, 500 mg per every day for eleven days for the treatment of glaucoma. Laboratory studies showed leukocyturia, thrombocytopenia, severe anemia, and tarry stools. The serum concentration of AZ was elevated to a maximum of 76.5 mg/ml. She was thus diagnosed as having AZ intoxication. On further examination, acute extensive hemorrhagic gastritis was also found by gastroscopy. Despite of the administration of intensive therapies, she died of disseminated intravascular coagulation (DIC) and septic shock due to bone marrow depression 6 days after admission. It is generally known that excessive blood levels of AZ inhibit not only the gastric juices but also prostaglandin levels and HCO3- excretion in the gastric mucosal barrier. We thus concluded that an excessive dose of AZ had probably destroyed the gastric mucosal barrier or thrombocytopenia due to bone marrow disorder and thus eventually led to the development of hemorrhagic gastritis. As far as we know, this is the first case report of acute hemorrhagic gastritis associated with AZ intoxication. Even though AZ tends to strongly bind to plasma protein and its clearance is generally poor by hemodialysis (HD), in our patient, HD was observed to be rather effective since the clearance of AZ was 45.8 ml/min on HD and 66 ml/min on direct hemoperfusion (DHP). DHP often reduces the number of platelets, also DHP needs a lot of heparin, therefore, we should have performed HD alone instead of DHP. In patients with an impaired renal function, AZ should therefore be administered very carefully in order to avoid an accumulation of the drug. In addition, HD alone should be used to remove any excessive amounts of AZ from the blood.
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PMID:Acute hemorrhagic gastritis associated with acetazolamide intoxication in a patient with chronic renal failure. 935 64

alpha-Agonists are a relatively old class of medications, the topical use of which lowers eye pressure. Clonidine was introduced for this use in 1966, brimonidine in 1974, and apraclonidine in 1978. Initial short-term attempts to use clonidine were complicated by problems with systemic hypotension. Apraclonidine is more polar and less lipophilic than clonidine. This probably allows less penetration into both the posterior segment of the eye and systemic circulation, allowing for an excellent therapeutic index. The prophylactic use of apraclonidine (1% and 0.5%) has dramatically changed the safety profile for many anterior segment laser procedures, cataract surgery, and vitrectomy. The role of alpha-agonists in the chronic treatment of glaucoma is still uncertain. Potential benefits of additional lowering of intraocular pressure must be weighed against the following potential disadvantages: tachyphalaxsis, posterior segment vasoconstriction, psychologic depression and fatigue, syncope and systemic hypotension, and a topical allergy-like syndrome.
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PMID:The role of alpha-agonists in glaucoma therapy. 1016 56

The purpose of this study was to correlate potential mechanisms with site(s) of action for TNPA-induced ocular hypotension. In response to R(-)-2, 10, 11-trihydroxy-N-propyl-noraporphine hydrobromide (TNPA, 75 microg), a D2 dopamine receptor agonist, the intraocular pressure decreased by 4.5 and 8 mm Hg at 1 and 2 hr, respectively, as measured by pneumatonometry. The levels of norepinephrine in aqueous humor, as determined by high performance liquid chromatography with electrochemical detection, were reduced by 38% and 79% at 1 and 2 hr, respectively, following topical application of TNPA (75 microg). Following pretreatment with raclopride (750 microg), a D2 receptor antagonist, and a subsequent challenge with TNPA (75 microg), the depression of intraocular pressure and levels of norepinephrine induced by TNPA (75 microg, 2 hr) were antagonized. In order to examine sites of action, immunohistochemistry of D2 dopamine receptors was performed in the ciliary body of normal and sympathetically denervated rabbits utilizing a goat polyclonal D2 receptor IgG and anti-goat IgG-FITC. Results from immunolocalization experiments demonstrated that D2 receptors are present on postganglionic sympathetic nerves in the ciliary body of normal rabbits but minimally detectable in that of sympathectomized rabbits. It is concluded that immunohistochemical identification of D2 receptors in the ciliary body associated with the suppression of aqueous norepinephrine levels by topical application of the D2 receptor agonist, TNPA, provide strong evidence of prejunctional (neuronal) site of action of TNPA. Antagonism of TNPA-induced ocular hypotension by raclopride coupled with the immunohistochemical and norepinephrine data suggest that D2 dopamine receptors are located on postganglionic sympathetic neurons in the ciliary body.
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PMID:Potential sites of action of TNPA: a dopamine-2 receptor agonist. 1062 Mar 90

Various classes of compounds exist to lower intraocular pressure (IOP) in the treatment of glaucoma. None of them is ideal since some patients respond better than others and the side effects vary between individuals. New classes of compounds need to be introduced to allow the clinician greater scope for effective treatment of all patients. It is now generally agreed that the cause of ganglion cell dysfunction in glaucoma is likely to be multifactorial and that concentrating solely on reducing IOP is inadequate. Irrespective of the reason for the dysfunction, the future goal must be to attenuate cell death. This may be achieved with drugs that interact with components of the retina, and is termed 'neuroprotection'. Thus, drugs that can both reduce IOP and act as neuroprotectants would be ideal for the treatment of glaucoma. In this article we summarise studies on animals which show serotonergic 5-HT1A agonists to both reduce IOP when topically applied to the rabbit eye and blunt the damaging effect to the rat retina and ganglion cells induced by glutamate toxicity or ischaemia. Reduction of IOP occurs via stimulation of 5-HT1A receptors associated with the ciliary processes. Neuroprotection of retinal neurones appears to involve the interaction of 5-HT1A agonists with membrane sodium channels and/or 5-HT1A or even possibly 5-HT7 receptors. Various 5-HT1A agonists are used in patients to treat depression, so classes of these drugs have a proven safety profile for use in patients. The animal studies summarised in this article suggest that 5-HT1A agonists need to be considered as a new class of drugs for the treatment of glaucoma.
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PMID:5-Hydroxytryptamine1A agonists: potential use in glaucoma. Evidence from animal studies. 1102 74


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