ABSTRACT
Corneal application of enalkiren (ABBOTT-64662), [N-(3-amino-3-methyl-1- oxobutyl)-4-methoxy-L-phenylalanyl]-N-[1S,2R,3S)-1-(cyclohexylmethyl+ ++)-2,3- dihydroxy-5-methylhexyl]-L-histidinamide], a renin inhibitor compound, lowered intraocular pressure (IOP) in unanesthetized rabbits and anesthetized monkeys. IOP was significantly decreased for at least 60 minutes after administration of a 0.3% solution of enalkiren in monkeys and for at least 90 minutes after the administration of 0.1% and 0.3% solutions in rabbits. Enalkiren did not affect systemic blood pressure or heart rate in anesthetized monkeys after topical application to the cornea. The IOP lowering activity of enalkiren suggests a potential functional role for the renin angiotensin system in the modulation of IOP.
Subject(s)
Dipeptides/pharmacology , Intraocular Pressure/drug effects , Renin/antagonists & inhibitors , Administration, Topical , Analysis of Variance , Animals , Blood Pressure/drug effects , Cornea , Dipeptides/administration & dosage , Heart Rate/drug effects , Macaca fascicularis , Male , RabbitsABSTRACT
Captopril, an angiotensin II converting enzyme (ACE) inhibitor, was evaluated for potential antidepressive activity on the forced swim-induced behavioral despair (immobility) test in mice. Captopril (10.0 and 30.0, mg/kg ip) significantly reduced immobility and mimicked the effects of the antidepressants imipramine (30.0 mg/kg, ip) and mianserin (3.0, 10.0, and 30.0 mg/kg, ip). Captopril increased the motor activity of mice at these same dosages. Naloxone (2.0 mg/kg, ip) blocked the effects of captopril (30.0 mg/kg, ip) in the swim test. These data suggest that captopril has potential antidepressive activity. However, the conclusion is guarded, as the positive effects may be related to motor stimulation. The blockade of the captopril effects by naloxone suggests that brain opioid peptides play a role in this behavioral effect of captopril.
Subject(s)
Arousal/drug effects , Captopril/pharmacology , Escape Reaction/drug effects , Motivation/drug effects , Animals , Dose-Response Relationship, Drug , Imipramine/pharmacology , Methamphetamine/pharmacology , Mianserin/pharmacology , Mice , Mice, Inbred Strains , Naloxone/pharmacology , SwimmingABSTRACT
Seven N-substituted 1,2,3,4-tetrahydro-1- and three 2-naphthylamines were prepared and tested for local anesthetic activity in the rabbit corneal reflex test and the mouse sciatic nerve block test. At 0.1 and 1%, three 1-alkylamino compounds had durations of action comparable to that of tetracaine in the rabbit corneal reflex test and were considerably more potent than lidocaine. The other four 1-alkylamino derivatives were inactive or at best minimally active. The durations of action of 1% concentrations of the three 2-alkylamino compounds were equivalent to that of 1% lidocaine in the corneal reflex test. In the mouse sciatic nerve block test, the three active 1-alkylamino compounds were considerably longer acting than either tetracaine or lidocaine. Three 1-alkylamino and the three 2-alkylamino compounds showed toxicity equal to or greater than lidocaine, while two 1-alkylamino and two 2-alkylamino compounds showed toxicity equal to or greater than tetracaine by the intraperitoneal route in mice. N-Heptyl-1,2,3,4-tetrahydro-6-methoxy-1-naphthylamine methanesulfonate was the most promising local anesthetic in these series.
