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Biomedical subjects

G Prat

Publications and source records attributed to G Prat.

At least 19 recordsLinked to original sources

[Sublingual captopril versus nifedipine in the treatment of hypertensive crisis].

The currently accepted drug of choice for treatment of hypertensive crisis is sublingual nifedipine. We compared the effects of sublingual captopril (25 mg) to those of nifedipine (10 mg) in 54 patients with this complication who came to the emergency room. Five min after administration of captopril, blood pressure decreased from 197.5 +/- 32.7/118.3 +/- 8.2 to 156 +/- 27.2/95.8 +/- 12.9 mmHg and heart rate decreased from 87.9 +/- 15.1 to 74.7 +/- 10.9 (p < 0.05). Blood pressure in the nifedipine group decreased from 198 +/- 27.3/120 +/- 9.8 to 147.7 +/- 17.8/86 +/- 17.9 (p < 0.05), while no change was observed in heart rate. Delayed measurements showed lower diastolic pressures at 60 and 75 min and lower systolic pressure at 120 min in the nifedipine group (p < 0.054). Few and not significantly different side effects were observed with both drugs. Thus, sublingual captopril is useful for treatment of hypertensive crisis.

Administration, Sublingual

T-maze performance in rats following chronic neuroleptic treatment.

The effects of chronic haloperidol treatment (0.5 mg/kg/day for 21 days) on maze learning in the rat were studied. There were no differences between haloperidol- and saline-treated groups in percentage of correct responses, but the latency to respond was longer and extinction was faster in the haloperidol-treated group. We speculated that differences between both groups were due to a decrease of appetitive motivation in haloperidol-treated animals, probably caused by a decrease of dopaminergic neurotransmission.

Animals

Is experimental catalepsy properly measured?

Following logarithmic transformation (ln) of total duration of haloperidol-induced catalepsy in the rat, measured by means of the bar test, a normalization of the results is achieved. With the help of this transformation we have been able to study what are probably the most important variables involved in the measuring of experimental catalepsy and to establish some criteria for a better use of such measures: 1) repeated measures of catalepsy have to be taken in order to avoid the stress-induced inhibition of catalepsy caused by the new experimental situation, 2) the dose of neuroleptic used has to be sufficiently low to permit the measurement of total or real duration of catalepsy between two determinations, and 3) the dose of neuroleptic has to be sufficiently high to prevent the development of a learned "pseudocatalepsy."

Adrenal Glands

Conditioning of rotational behavior after the administration of a single dose of apomorphine in rats with unilateral denervation of the dopaminergic nigrostriatal pathway: relevance to drug addiction.

Our aim is to study the relationship of drug activation of the dopamine neurotransmission system and the conditioning of environmental stimuli present at the time of drug administration. We injected a single dose of apomorphine (0.05 mg/kg SC) in rats with the nigrostriatal dopamine pathways unilaterally denervated with 6-hydroxydopamine, which generates rotational behavior contralateral to the lesioned hemisphere. We observed rotational behavior without apomorphine administration when animals were reexposed at different time intervals to the same environment in which they performed turning behavior. The present findings show that this rotational behavior can be conditioned to environmental stimuli in a strong and long-lasting way. In light of the relationship between opioids and the dopaminergic system, similar conditioning could take place in the learning processes implicated in drug addiction.

Animals

Metabolism of thymoxamine: identification of metabolites in rat.

Thymoxamine hydrochloride administered by mouth to rats at 25 or 100 mg kg-1 was excreted in the urine as the deacetyl and N-demethyl-deacetyl metabolites. These were completely sulpho- and glucuronoconjugated at 25 mg kg-1 but only partially so at the higher dose. Thymoxamine deacetylation in vitro is catalysed by plasma and hepatic cytosol esterases and the deacetyl metabolite undergoes N-demethylation catalysed by the cytochrome P 450 hepatic microsome mixed function monooxygenase system. Because of the rapidity of the deacetylation it is concluded that thymoxamine is a prodrug leading in vivo to the active deacetyl thymoxamine.

Animals

In vitro and in vivo alpha-blocking activity of thymoxamine and its two metabolites.

The alpha-adrenoceptor potency of thymoxamine and its two metabolites deacetylthymoxamine and demethyldeacetylthymoxamine were determined on the contraction of rat vas deferens induced by noradrenaline, the blood pressure increase induced by noradrenaline given i.v. to dogs and the contraction of the nictitating membrane induced by electrical stimulation in cats. In vivo the three drugs were administered at 6.35 x 10(-6) mol kg-1 intravenously. Deacetylthymoxamine presented nearly the same alpha-blocking activity as the parent drug. This was ascribed in vivo to the rapid deacetylation of thymoxamine. Demethyldeacetylthymoxamine was less active. In vitro its pA2 was 6.20 +/- 0.09 compared with 6.75 +/- 0.20 for thymoxamine and 6.57 +/- 0.13 for deacetylthymoxamine. In vivo, it was inactive in dog and less active than the other two drugs soon after its administration in the cat. The oral LD 50 values in the mouse for the three drugs were respectively 0.81, 0.71 and 1.14 mmol kg-1 for thymoxamine, deacetylthymoxamine and demethyldeacetylthymoxamine.

Adrenergic alpha-Antagonists