Analgesic and anti-inflammatory activity of 10-amino-11H-indeno [1,2-b] quinolin-11-one derivatives.

Ten novel derivatives of 11H-indeno [1,2-b] quinolin-11-one (1-10) were synthesized and pharmacologically screened. All compounds showed analgesic activity. Anti-inflammatory activity was found only for alkylamine derivatives 1-6. The most active 10-ethylamine derivative 2 showed also ulcerogenic properties. The LD50/UD50 and UD50/ED50 values for compound 2 were less satisfactory than those for ibuprofen.

Absence of reinforcement with low dose intravenous ethanol self-administration in rats.

Male hooded rats were implanted with intravenous cannulas and housed in operant chambers supplied with 2 levers and enclosed in sound-attenuating cubicles. In Experiment 1, seven rats received a 1.0 mg/kg infusion of ethanol for each press on the previously determined non-preferred lever. The other lever served to count "activity lever presses." An additional 7 rats served as controls and were treated identically except that each press on the non-preferred lever led to an infusion of saline, isovolumetric to the ethanol infused in the experimental subjects. The rats were tested under these conditions of continuous reinforcement for 9 days. Throughout this period, self-infusions and "activity lever presses" did not differ between the groups, suggesting that ethanol was not reinforcing at a dose of 1.0 mg/kg. These results were replicated, and extended to other low doses of ethanol in Experiment 2. Here, we employed a design where depression of either lever, under conditions of continuous reinforcement, led to the infusion of a solution. Fifteen rats were randomly assigned to one of three groups (5 rats/group). In one group, depression of the previously determined non-preferred lever led to an infusion of 16.0 mg/kg of ethanol, while depression of the other lever led to an infusion of isocaloric glucose. For the other two groups, depression of the non-preferred level led to an infusion of 4.0 and 1.0 mg/kg ethanol respectively, and depression of the other lever led to a glucose infusion. The animals were tested for 9 days, and in each case, ethanol self-infusions did not differ significantly from glucose self-infusions.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of two intravenous infusion schedules for inducing physical dependence upon ethanol in rat.

Male hooded rats were implanted with intravenous (IV) cannulas and housed in operant chambers. The effectiveness of two infusion schedules for producing physical dependence upon ethanol was assessed. Twenty-three rats (12 ethanol, 11 control) were tested under a 4 hr interinfusion schedule (one infusion every 4 hr, around the clock), and 29 rats (15 ethanol, 14 control) were tested under a 2 hr interinfusion schedule. During the dependence induction phase, which lasted for 6 days, the experimental rats received ethanol (30% v/v) at an average daily dose which ranged from 8.4-11.8 g/kg, and the dose administered per infusion was adjusted according to the degree of intoxication of each animal. The pair-fed control subjects received infusions of isocaloric control solutions (either 29% v/v propylene glycol or 31% v/v glycerol). Following the dependence induction phase, ethanol was withdrawn, and withdrawal symptoms were assessed. Blood ethanol levels (BEL) and signs of intoxication were determined through all phases of the experiment. During the dependence induction phase, mortality was close to zero, and weight loss was held to about 10%. Tolerance to ethanol developed in all experimental rats. During the withdrawal period, all ethanol rats developed clear withdrawal symptoms, while control subjects did not. Ethanol elimination rates ranged between 45-50 mg/dl/hr and withdrawal symptoms began when BEL fell below 200 mg/dl, and were severe when BEL approached zero. The 2 hr schedule proved superior to the 4 hr schedule in that it led to greater stability of BEL during dependence induction, and a tendency for the withdrawal reaction to be more severe.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacological properties of the antiinflammatory agent 10-methylamine-11-H-indeno-[1,2-b]quinolin-11-one (MB432).

10-Methylamine-11-H-indeno [1,2-b] quinolin-11-one (MB432) was found to be a prostaglandin synthetase inhibitor, to display antiinflammatory activity in carrageenin edema and cotton pellet granuloma tests in rats, and to exert analgesic action in paw pressure test in rats and in the writhing test in mice. The therapeutic index (LD50/ED50) for antiinflammatory and analgesic effect of MB432 is higher than that of indomethacin (IND) and phenylbutazone (PHB). The acute toxicity of MB432 is low but the drug showed high ulcerogenic activity. The ratio of medium ulcerogenic to median antiinflammatory and analgesic doses of MB432 is comparable to that of PHB but higher than for IND.

Pharmacological properties of new 11H-indeno[1,2-b]-quinolin-11-one derivatives.

Pharmacological properties of 7 new 11H-indeno [1,2-b]quinolin-11-ones (1-7) were investigated in mice and rats. For comparison indomethacin (IND) and phenylbutazone (PHB), were studied. Compounds 1 and 3-7 produced sedative action. Compound 2 had a stimulatory effect. IND and PHB did not affect the central nervous system. All tested compounds showed analgesic properties, similar to those of IND and more pronounced than those of PHB. Compounds 1, 2, 3, 4 had anti-inflammatory action. The most active of them 10-methyl-amine derivative (compound 2) was more effective than IND and PHB.

Synthesis and pharmacological screening of some N-carboxymethylbarbituric acid derivatives. I.

Reaction of haloacetate with barbital and methylphenobarbital in polar aprotic solvents in the presence of anhydrous K2CO3 gave N-carboalkoxymethyl derivatives in good yields. Acidic hydrolysis of the latter compounds affords N-carboxymethyl derivatives of barbital 8 or methylphenobarbital 7. From acid 7 and 8 via acid chlorides, amides 11--20 were prepared. These amides lack anticonvulsant activity and show only slight sedative and analgesic action.