Disminución de la agudeza visual tras un procedimiento odontológico: A propósito de un caso / Unilateral visual impairment after a dental procedure: Case report

El uso de anestésicos locales para la realización de procedimientos odontológicos es una práctica ampliamente extendida que puede causar efectos adversos. Sin embargo, muy infrecuentemente puede causar complicaciones oculares como diplopía, ptosis, visión borrosa, miosis, disminución de la agudeza visual o amaurosis. Presentamos un caso de un paciente varón de 26 años que se presentó a la consulta por una disminución de la agudeza visual en su ojo derecho 48h después de una intervención odontológica del lado ipsilateral, logrando una recuperación de la misma en los 6 meses posteriores, sin tratamiento alguno. Diferentes teorías que justifiquen la aparición de complicaciones oculares como consecuencia de esta clase de procedimientos han sido propuestas en la literatura. En nuestro caso, una inyección intravenosa inadvertida habría sido la causa posible del hecho (AU)

The use of intra-oral local anaesthetics for dental procedures is a widely extended practice that may cause side effects. As such, in rare cases it may cause ocular complications such as diplopia, ptosis, blurry vision, miosis, vision loss, or amaurosis. (Most of them are transient, recovering after several hours or days). A case is presented of a 26 year-old male patient who had visual impairment in the right eye 2 days after a dental procedure was performed. Six months later he had a complete restoration of the previous visual acuity, despite the fact that he had not received any treatment. Several ways have been proposed in the literature that may explain the appearance of ocular complications following these kinds of procedures. In this case, inadvertent intravenous injection is believed to have been the cause (AU)

Unilateral visual impairment after a dental procedure: Case report.

The use of intra-oral local anaesthetics for dental procedures is a widely extended practice that may cause side effects. As such, in rare cases it may cause ocular complications such as diplopia, ptosis, blurry vision, miosis, vision loss, or amaurosis. (Most of them are transient, recovering after several hours or days). A case is presented of a 26 year-old male patient who had visual impairment in the right eye 2 days after a dental procedure was performed. Six months later he had a complete restoration of the previous visual acuity, despite the fact that he had not received any treatment. Several ways have been proposed in the literature that may explain the appearance of ocular complications following these kinds of procedures. In this case, inadvertent intravenous injection is believed to have been the cause.

Unilateral visual impairment after a dental procedure: Case report. / Disminución de la agudeza visual tras un procedimiento odontológico: A propósito de un caso.

The use of intra-oral local anaesthetics for dental procedures is a widely extended practice that may cause side effects. As such, in rare cases it may cause ocular complications such as diplopia, ptosis, blurry vision, miosis, vision loss, or amaurosis. (Most of them are transient, recovering after several hours or days). A case is presented of a 26 year-old male patient who had visual impairment in the right eye 2 days after a dental procedure was performed. Six months later he had a complete restoration of the previous visual acuity, despite the fact that he had not received any treatment. Several ways have been proposed in the literature that may explain the appearance of ocular complications following these kinds of procedures. In this case, inadvertent intravenous injection is believed to have been the cause.

Gastroprokinetic properties of the benzimidazolone derivative BIMU 1, an agonist at 5-hydroxytryptamine4 and antagonist at 5-hydroxytryptamine3 receptors.

We have investigated the in vivo motor stimulating and gastroprokinetic properties of the azabicycloalkyl benzimidazolone derivative BIMU 1 (3-ethyl-2,3-dihydro-N-(8-methyl-8-azabicyclo[3.2.1]oct-3-yl)-2-oxo-1H- benzimidazole-1-carboxamide hydrochloride) and its binding profile at 5-hydroxytryptamine3 and 5-hydroxytryptamine4 receptors, in an attempt to assess the serotonergic mechanism underlying its prokinetic action. BIMU 1 dose-dependently (0.01-0.3 mg/kg i.v.) increased the motility of a denervated pouch of canine stomach. This excitatory action was sensitive to muscarinic blockade. A similar stimulatory effect was exerted by the benzamidic prokinetic agent cisapride (0.03-0.3 mg/kg i.v.) but not by the 5-HT3 receptor antagonist ondansetron (up to 1 mg/kg i.v.). The significance for propulsive efficacy of the motor stimulating activity of BIMU 1 was evaluated in a model of gastric emptying of liquids in the conscious dog. The emptying rate of a non-caloric liquid meal instilled through a gastric fistula was accelerated by both BIMU 1 (0.01-1 mg/kg i.v. and 0.1-3 mg/kg p.o.) and cisapride (0.03-1 mg/kg i.v. and 0.3-10 mg/kg p.o.). Ondansetron (1 mg/kg i.v.) did not show any effect. The activity of the 5-HT4 receptor antagonist DAU 6285 was evaluated in the gastric emptying model per se and in interaction experiments on the accelerating action of BIMU 1 (0.3 mg/kg i.v.).(ABSTRACT TRUNCATED AT 250 WORDS)

Characterization of a novel 5-HT4 receptor antagonist of the azabicycloalkyl benzimidazolone class: DAU 6285.

Three chemical classes of serotonin 5-HT4 receptor agonists have been identified so far: 5-substituted indoles (e.g. 5-HT), benzamides (e.g. renzapride) and benzimidazolones (e.g. BIMU 8). In a search for 5-HT4 receptor antagonists, we have discovered that the benzimidazolone derivative DAU 6285 (for structure see text), is 3-5 times more potent than tropisetron in blocking 5-HT, renzapride and BIMU 8 induced stimulation of adenylate cyclase activity in mouse embryo colliculi neurons. Schild plot analysis yielded Ki values of 220, 181 and 255 nmol/l, respectively. In addition, DAU 6285 showed poor activity as a 5-HT3 receptor ligand with respect to tropisetron, as demonstrated by in vitro binding studies (Ki, 322 vs 2.8 nmol/l) and by its antagonistic activity in the Bezold-Jarisch reflex test (ID50, 231 vs 0.5 micrograms/kg, i.v.). No significant binding (Ki greater than 10 mumol/l) of DAU 6285 to serotonergic 5-HT1A, 5-HT1B, 5-HT1C, 5-HT1D, and 5-HT2 receptors as well as to adrenergic alpha 1, alpha 2, dopaminergic D1, D2 or muscarinic M1-M3 receptor subtypes was found. The data indicate that DAU 6285 has a somewhat higher affinity than tropisetron for 5-HT4 receptors, a property confirmed in functional tests, and much lower affinity than tropisetron for 5-HT3 receptors. The compound represents a new interesting tool for investigating the pharmacological and physiological properties of 5-HT4 receptors.

Antiemetic activity of the new 5-HT3 antagonist DAU 6215 in animal models of cancer chemotherapy and radiation.

The antiemetic activity of DAU 6215, a novel antagonist of 5-HT3 receptors, was investigated in animal models of cytotoxic treatment-evoked emesis and compared with the antiemetic activity of ondansetron and metoclopramide. In dogs, vomiting was induced by i.v. cisplatin; in ferrets, the emetic response was elicited by i.v. doxorubicin or X-ray exposure. Pretreatment with 0.1-1 mg/kg DAU 6215 given i.v. or p.o. prevented the vomiting response to the different emetic agents. In the dog, the antiemetic potency of metoclopramide was 30 times lower than that of DAU 6215. Ondansetron was less potent than DAU 6215 against cisplatin and doxorubicin but was equally effective in the radiotherapy protocol. In this model, lengthening of the pretreatment time to 2 h did not affect the antiemetic efficacy of DAU 6215, whereas it decreased that of ondansetron. The results demonstrate that DAU 6215 is a highly effective and long-lasting inhibitor of cytotoxic treatment-induced emesis in different animal species.

Pharmacological activity of bamifylline on lung anaphylaxis: in vitro studies.

Bamifylline, a 7-8 disubstituted theophylline derivative, reduces in a dose dependent way (1 x 10(-5) M, 1 x 10(-4) M and 1 x 10(-3) M) the release of histamine, TXB2 (measured also as TXA2-like material) and SRS-A (as LTD4-like material) during the immunological challenge of actively sensitized guinea-pig lungs perfused in vitro. Theophylline was significantly less potent than bamifylline and particularly, at the higher concentrations used (1 x 10(-3) M), bamifylline was 2.7 times more potent than theophylline in reducing the immunological release of histamine and 1.6 and 1.5 times more potent in inhibiting the production of TXB2 and SRS-A, respectively. These data suggest that the ability of the two xanthine derivatives to control the immunological release of histamine represents an important point in understanding the mechanism of their anti-anaphylactic activity.

[Chemistry and pharmacology of pyrane derivatives. XVII. Synthesis of substituted 2-(dialkylamino)-3-formylchromones and their tricyclic derivatives]. / Ricerche chimiche e farmacologiche su derivati piranici nota XVIII - sintesi di 2-(dialchilammino)-3-formilcromoni sostituti e di loro derivati triciclici.

Substituted 2-(dialkylamino)-3-formylchromones (II) were obtained from the reaction of substituted 2-(dialkylamino)chromones (I) either with the N,N-dimethylformamide-POCl3 reagent [compounds (IIa-e)] or with dichloromethylmethylether in the presence of TiCl4 [compounds (IIf-i)]. By treating (IIa,f) with hydroxylamine the oximes (IIIa,f) were prepared, which in turn were converted into the nitriles (IVa,f) by treatment with acetic anhydride. Compound (IIa), selected for the smallest steric hindrance of the 2-dialkylamino substituent, by reaction with hydrazines afforded [1]benzopyrano [2,3-c]pyrazole derivatives (VI), whereas reaction of (IIa) with guanidine, benzamidine or S-methylisothiourea gave rise to the formation of 5H-[1]benzopyrano[2,3-d]pyrimidine derivatives (IX). Among the compounds tested for their antiallergic properties, (IIf) showed an appreciable activity, but also high toxicity.

Evidence of pulmonary tropism of bamifylline and its main active metabolite.

The extent of the extraplasmatic tropism of bamifylline (Bamifix) was evaluated in the rat and in man by assaying concentrations of bamifylline and of its main active metabolite AC-119 in lung tissue and plasma. After a single oral and intravenous administration of bamifylline in the rat, the ratio between pulmonary and plasma concentrations was between 2.0 and 3.2 for bamifylline, and between 4 and 15 for AC-119 during the observation period considered. On the other hand, the same ratios, calculated after the oral and intravenous administration of theophylline, ranged between 0.20 and 0.39. In studies on man, samples of plasma and lung tissue were obtained during surgery in subjects affected by pulmonary neoplasia and previously subjected to therapy with bamifylline according to the usual dosage scheme. The ratios between tissue and plasma concentrations, at the steady-state and in conditions of equilibrium between the compartments, were 9.4 for bamifylline and 34.7 for its active metabolite. The particular tissue tropism of bamifylline, that appears to be due to its high lipophilic character, could partly explain its high therapeutic index.

[Derivatives of pyrimidine 1,2-condensate. IV. Synthesis and pharmacological properties of the N,N-disubstituted 4-amino-2H-pyrido(1,2-a)pyrimidin- 2-ones and 2-amino-4H-pyrido(1,2-a)pyrmidin-4-ones]. / Derivati di pirimidine 1,2-condensate. Nota IV--Sintesi e proprietà farmacologiche di 4-ammino-2H-pirido[1,2-a]pirimidin-2-oni e 2-ammino-4H-pirido[1,2-a]pirimidin-4-oni N,N-disostituiti.

The N,N-disubstituted 4-amino-2H-pyrido[1,2-a]pyrimidin-2-ones (III) and isomer 2-amino-4H-pyrido[1,2-a]pyrimidin-4-ones (IV) were obtained from the reaction of 2-aminopyridine with the N,N-disubstituted ethyl malonamate/phosphorus oxychloride reagent (II), in refluxing 1,2-dichloroethane. 2-[(N-Benzyl, N-ethyl)amino]derivative (IV b) was also prepared in excellent yield by treating 2-chloro-4H-pyrido[1,2-a]pyrimidin-4-one (V) with N-ethylbenzylamine. Finally, hydrogenation (Raney Nickel) of 4-[(N-ethyl,N-phenyl)amino]-2H-pyrido[1,2-a]pyrimidin-2-one (III e) afforded 6,7,8,9-tetrahydroderivative (VI) which in turn was treated with potassium borohydride to give 1,6,7,8,9,9a-hexahydroderivative (VII). Several compounds described in the present paper, along with some other compounds (III) and (IV) previously synthesized by us (1,2), were tested for various pharmacological activities. The antiallergic activity (PCA in the rat), even though found in several compounds examined, turned out to be submaximal in any case, in spite of the high dose administered (500 mg/kg p.o. as a rule). The most active compound (the activity being estimated at 0.42 times that of thiaramide hydrochloride) was the 4-aminoderivative (III e). The 2-aminoderivatives (IV) series, was found to have marked antiinflammatory properties (carrageenin oedema in the rat); nevertheless, this activity was related to toxic symptoms with the exception of compound (IV b), almost asymptomatic at the administered dose (200 mg/kg p.o.). Moreover the 2-aminoderivatives (IV) generally showed weak adrenolitic activity in vitro (rat seminal vesicles), which was estimated to be from 100 to 1000 times less than that of phenoxybenzamine.

New pharmacological data on the bronchospasmolytic activity of bamifylline.

Resistance to lung inflation and blood pressure were monitored together with biological and radioimmunological determination of circulating thromboxane A2 (TxA2) in anaesthetized guinea-pig. Bamifylline, a 2-benzyl-[4,5-d]-imidazopyrimidine derivative, and theophylline were compared for their antagonistic activity against the pulmonary effect of histamine (0.05 mumol/kg i.v.), leukotriene C4 (LTC4, 0.016 mumol/kg i.v.), platelet-activating factor (PAF, 0.0002 mumol/kg i.v.) and acetylcholine (0.1 mumol/kg i.v.). Bamifylline, as well as theophylline, showed a dose-dependent antagonistic activity against both bronchoconstriction and TxA2 generation induced by the above agonists. However, except for histamine where the two compounds were equiactive, bamifylline was 2 times more potent than theophylline. The maximal inhibitory activity was found against bronchoconstriction induced by PAF (ED50 = 6.5 mumol/kg i.v.) followed by histamine (ED50 = 9.5 mumol/kg i.v.), acetylcholine (ED50 = 24.3 mumol/kg i.v.) and LTC4 (ED50 = 31.6 mumol/kg i.v.). Bamifylline (3, 10, 30, 100 mumol/kg i.v.) and theophylline (3, 10, 30, 100 mumol/kg i.v.) protected guinea-pig from antigen-induced bronchoconstriction and TxA2 generation in ovalbumin actively sensitized animals. Also in this series of experiments bamifylline was more potent than theophylline, the ED50 being 9.3 mumol/kg i.v. and 22.9 mumol/kg i.v., respectively. These pharmacological data represent new support for the protecting effect of bamifylline against respiratory damage induced by well known anaphylaxis mediators.

[Chemistry and pharmacology of pyran derivatives. XVII. Synthesis of 2-(dialkylamino)-5-hydroxychromones and their transformation to derivatives of 2H-pyran[4,3,2-de]-1-benzopyran]. / Ricerche chimiche e farmacologiche su derivati piranici. Nota XVII. Sintesi dei 2-(dialchilammino)-5-idrossicromoni e loro trasformazione in derivati del 2H-pirano [4,3,2-de]-1-benzopirano.

Through the reaction of resorcin with N,N-dialkylethoxy-carbonylacetamides in suitable conditions 2-(dialkylamino)-5-hydroxychromones (II) were available. Transformation of these compounds into [5-acetoxy-2-(dialkylamino)-4H-chromen-4-ylidene] malononitriles (VII) by reaction with malononitrile in acetic anhydride and treatment of (VII) with hydrochloric acid gave rise to the formation of 5-(dialkylamino)-2-imino-2H-pyrano [4,3,2-de]-1-benzo-pyrans (VIII). Furthermore 5-hydroxychromones (II) when treated with methyl iodide gave the corresponding 5-methoxychromones (III) which in turn yielded 4H-chromen-4-ylidene derivatives (X) by reaction with malononitrile in acetic anhydride. The hydrolysis of the latter compounds with hydrochloric acid resulted in the formation of 2-(dialkylamino)-4-methyl-5-methoxychromenilium salts (XI). Among the compounds which were submitted to pharmacological screening for their antiallergic properties 5-methoxychromone (III a) and 2H-pyrano [4,3,2-de]-1-benzopyran (VIII b) showed a notable activity but also high toxicity.

[Chemistry and pharmacology of pyran derivatives. 16. Derivatives of 2-(dialkylamino)-7-methoxychromone with antiallergic activity]. / Ricerche chimiche e farmacologiche su derivati piranici. Nota XVI. Derivati del 2-(dialchilammino)-7-metossicromone ad attività antiallergica.

Since 2-(diethylamino)-7-methoxychromone (III a) showed remarkable activity in the rat PCA test, some modifications to its structure were made. For instance new substituents such as chlorine or nitro group were introduced into the molecule and the diethylamino group modified. Thus, 2-(ethylamino)-7-methoxychromone (IX) was prepared by treating 3-methoxyphenol with N-ethylethoxycarbonylacetamide in the presence of phosphorus oxychloride. In this case a small amount of 4-chloro-7-methoxycoumarin was also isolated from the reaction mixture. Moreover compounds (XIV), (XV), (XVII) structurally related to sodium cromoglycate were prepared. The pharmacological screening of some compounds showed a useful antiallergic activity.

Cardiovascular effects of nicardipine in anesthetized open-chest dogs in the absence and presence of beta-adrenergic receptor blockade: a comparison with nifedipine and verapamil.

Nicardipine, a new 1,4-dihydropyridine calcium-entry blocker, was assessed for cardiovascular effects against nifedipine and verapamil in anesthetized open-chest beagle dogs, in the absence and presence of beta-adrenoceptor blockade (propranolol 1 mg/kg i.v.). In control conditions, intravenous nicardipine and nifedipine (30 nmol/kg) produced decreases in blood pressure of similar magnitude without evidence of cardiodepression. An equihypotensive dose of verapamil (300 nmol/kg), by contrast, induced long-lasting negative chronotropic and inotropic effects, which, when combined with the effects of propranolol, were so marked as to cause the death of two of five dogs (atrioventricular block). Dihydropyridine derivatives at higher doses (100 nmol/kg) produced different responses: nifedipine depressed cardiac performance significantly more than nicardipine and, in the presence of beta-adrenergic blockade, caused the death of three of six dogs due to cardiovascular failure. In the nicardipine group, on the contrary, cardiac function was adequately preserved even in the presence of beta-blocker, and no animals died. The results of the present study confirm a previous in vitro observation: nicardipine is a calcium-entry blocker devoid of remarkable cardiodepressant effects and particularly selective for the vascular smooth muscle.

Regional vasodilating and cardiac effects of nicardipine in anaesthetized open chest dog.

In this study the effects of intravenous nicardipine on the cardiovascular system in anaesthetized open chest dogs were assessed. In the dose range of 3-30 nmol/kg it induced a dose-dependent and long lasting reduction of the vertebral, coronary and femoral vascular resistance. Nicardipine proved to be equipotent, but longer lasting than nifedipine, and about 10 and 100 times more potent than verapamil and papaverine respectively. Unlike papaverine, calcium entry blockers caused a preferential vasodilation of the vertebral and coronary arteries. Hypotension and a reduction of LVSP and dP/dt appeared only at the highest dose tested. However, for both dihydropyridine derivatives, in contrast to verapamil, the cardiodepressant effects were short-lived and resulted less marked for nicardipine than for nifedipine.