RESUMO
This double-blind, placebo-controlled, randomized multicenter study evaluated the antihypertensive efficacy and safety of cetamolol hydrochloride in 108 patients diagnosed as having mild to moderate hypertension. After a placebo lead-in period, patients received either cetamolol 5-10-15 mg/d (low dose), cetamolol 15-25-50 mg/d (high dose), or placebo, once daily for four weeks. Patients began at the lowest dose and were titrated to higher doses based on the first two assessments of diastolic blood pressure and heart rate, which were conducted each week after double-blind treatment was dispensed. After four weeks of treatment 82.4%, 81.3%, and 93.3% of the low-dose group, high-dose group, and placebo group, respectively, were titrated to the maximum dose level. After four weeks of treatment and 24 hours since the patient's last dose, both cetamolol groups showed a significantly greater (P less than or equal to .05) reduction in supine systolic/diastolic blood pressure (-18.1 +/- 2.3/-9.2 +/- 1.5 mm Hg [low dose] and -17.3 +/- 2.3/-8.3 +/- 1.6 mm Hg [high dose]) than the placebo group (-9.9 +/- 2.5/-3.5 +/- 1.7 mm Hg). In general, the changes in standing (stabilized) systolic and diastolic blood pressure were similar to those seen in supine measurements. Significantly more patients receiving cetamolol than those receiving placebo showed a "good response" (a decrease in diastolic blood pressure of 10 mm Hg or more or measuring less than 90 mm Hg with a decrease of at least 4 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Acetamidas/uso terapêutico , Hipertensão/tratamento farmacológico , Acetamidas/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Ensaios Clínicos como Assunto , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Distribuição AleatóriaAssuntos
Química Encefálica/efeitos dos fármacos , Cálcio/fisiologia , Morfina/farmacologia , Adenilil Ciclases/metabolismo , Animais , Cálcio/metabolismo , Cálcio/farmacologia , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , AMP Cíclico/metabolismo , AMP Cíclico/fisiologia , Humanos , Magnésio/metabolismo , Dependência de Morfina/fisiopatologiaAssuntos
Cálcio , Naloxona/antagonistas & inibidores , Síndrome de Abstinência a Substâncias , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Cálcio/metabolismo , Cálcio/farmacologia , Humanos , Masculino , Morfina/farmacologia , Ratos , Síndrome de Abstinência a Substâncias/metabolismo , Transtornos Relacionados ao Uso de Substâncias/metabolismoRESUMO
The effect of amphetamine and l-dopa was compared in 22-hr food- and water-deprived rats. Amphetamine produced marked anorexia, and l-dopa significantly reduced food intake at 200 mg/kg. Following pretreatment with RO 4-4602, a decarboxylase inhibitor, 100 mg/kg of l-dopa, a dose that did not significantly affect eating, produced marked anorexia. The anorectic effect of both amphetamine and l-dopa was antagonized by propranolol, a beta adrenergic antagonist. Phentolamine, an alpha-adrenergic antagonist, potentiated the anorectic effect of amphetamine and l-dopa. Haloperidol (0.1 mg/kg), a dopamine antagonist, failed to prevent the anorexia due to amphetamine but accentuated that due to l-dopa. Methysergide, a serotonin antagonist, also failed to prevent the anorexigenic effect of amphetamine. Finally, the administration of l-dopa with or without peripheral decarboxylase inhibition resulted in more than twice the increase in hypothalamic dopamine levels without significant changes in 5-HT or norepinephrine levels. The data show that the anorexigenic effect of amphetamine and l-dopa are similar and indicate a functional role for both norepinephrine and dopamine neurons in feeding behaviour in the rat.
