Reactions of phthalimides with 1-methylethylamine: analgesic and anti-inflammatory properties of resulting carboxamides.

The reaction of phthalimide derivatives (1a-c) with 1-methylethylamine in dimethylformamide (DMF) at room temperature afforded benzamido-N-prop-2-ynyl-2-(2-methylethyl)-carboxamide (3a), benzamido-N-cyclopentyl-2-(2-methylethyl)-car-boxamide (3b) and benzamido-N-benzyl-2-(2-methylethyl)-carboxamide (3c), respectively. In the carrageenan induced paw oedema test for anti-inflammatory activity, 3a (50 mg/kg) decreased the inflammatory response by 55% after 3 hrs while 3b and 3c exhibited significant reduction in the oedema level. The compounds 3a, 3b and 3c exhibited analgesic activities with 3b producing 76% inhibition. The activities were dose - dependent.

Phytochemical and active column fractions of Pyrenacantha staudtii leaf extracts on isolated rat uterus.

Four methanolic leaf fraction extracts of Pyrenacantha staudtii obtained from accelerated gradient chromatography (AGC) were tested on the isolated rat uterus. Various fractions--M1, M2, M3 and M4 through bioassay guided isolation were obtained. Fractions M(2) and M(4), containing saponins and alkaloids respectively, significantly (P<0.05) exerted high smooth muscle relaxant activity on the uterus. Fractions M(1) and M(3) containing fatty acids and tannins respectively did not exhibit significant effect on the isolated rat uterus. The results indicate the presence of active principles in the leaf extracts of P. staudtii which may be responsible for some of the applications in traditional medicines as remedy against threatened abortion and dysmenorrheal.

Adsorptive Property of Kaolin in some Drug Formulations

PURPOSE: Kaolin is a known adsorbent; has lubricant property in powders and is therefore proposed as a lubricant in tablet formulations. This study was carried out to evaluate whether kaolin can adsorb some active drugs when mixed with them in tablet formulations even at very low concentrations. METHOD: Chloroquine and chlorpheniramine tablets were formulated with powder mixtures containing various concentrations of kaolin. The effect of kaolin on the physical properties of the tablets were examined and compared with those of standard lubricants like magnesium stearate and talc. Chloroquine and chlorpheniramine tablets and powders of amoxicillin/clavulanic acid oral powder and ampicillin/cloxacillin injection were also mixed with and without various concentrations of kaolin in water. Chemical assay of the drugs in the solutions were determined over time. RESULTS: Kaolin significantly reduced the amount of each of the drugs in the solutions containing kaolin. CONCLUSION: Kaolin reduces the amount of some drugs when incorporated in drug formulations. Therefore; its inclusion in such drug formulations should not be encouraged

Synthesis and anticonvulsant activity of N,N-phthaloyl derivatives of central nervous system inhibitory amino acids.

In order to study the influence of the length of the amino acid chain of N,N-phthaloyl-amino acid amides as analogues of the former anticonvulsant taltrimide on the seizure-antagonizing activity glycine, beta-alanine and gamma-aminobutyric acid (GABA) derivatives were synthesized. The corresponding taurine derivatives were also included. Generally, the glycine-derived amides showed a higher activity than the beta-alanine and GABA derivatives in the maximal electroshock seizure (MES) test in mice upon intraperitoneal administration. The activity was comparable to the respective taurine derivatives. The N,N-phthaloyl-glycine amides were also active in the MES test upon oral administration to rats. No significant activity was noted in the seizure threshold test with subcutaneous pentylene-tetrazole. The ED50 of N,N-phthaloyl-glycine ethyl amide (4b) in the MES test upon intraperitoneal administration to mice was 19.1 mg/kg. On a molar basis this activity is comparable to the activity of phenytoin with little toxicity in the rotorod test. In conclusion, N,N-phthaloyl-glycine amides might represent promising antiepileptic drugs.

Anticonvulsant activity of reaction products of 5,5-diphenylhydantoin with substituted methylene bromides.

Some derivatives of 5,5-diphenylhydantoin (phenytoin) were synthesized by the alkylation of phenytoin with substituted methylene bromides. The hydantoins were evaluated for possible anticonvulsant activity in the maximal electroshock (MES)- and subcutaneous pentylenetetrazole (ScMet)-induced seizures and for neurotoxicity in the rotorod test in mice and rats.

Synthesis and anticonvulsant activity of acetylenic quinazolinone derivatives.

Acetylenic derivatives of quinazolinones and quinazolinediones were synthesized and evaluated for their anticonvulsant activity. Most compounds displayed seizure-antagonizing activity in the maximal electroschock test (MES test) in most cases associated with little or no acute neurotoxicity determined in the rotorod test. Only three compounds exhibited significant activity in the seizure threshold test with subcutaneous pentylenetetrazole (scMet test). Based on the ED50 in the MES test, 1,3-bis-(prop-2-ynyl)-quinazoline-2,4-(1H,3H)-dione(9a) was about ten-fold less active than phenytoin or carbamazepine but about as active as mesuximide.

The impact of the Lagos manual vacuum aspiration (MVA) training courses on medical education.

The Department of Obstetrics and Gynaecology, College of Medicine, University of Lagos commenced training programmes in the use of manual Vacuum Aspiration (MVA) for the treatment of septic abortion in 1989. The courses were evaluated using pre-tests and post-tests, and those of the participants from the first 5 years were analysed. 142 doctors and 72 nurses were trained from teaching hospitals, parastatal and private hospitals. The results of 154 participants (71%) were recovered and analysed. The training courses significantly increased the medical knowledge of both doctors and nurses; those from the Teaching Hospitals appearing to gain more. The amount of knowledge gained by those from the private sector, although showing a statistically significant increase was much less than the other participants. More emphasis should be placed on improving the performance of those from the private sector.

A review of referred IUCD related problems in Lagos University Teaching Hospital.

A review of 168 patients referred with IUCD related problems was done. The two most common indications for referrals were difficulty at removal (73.8%) and missing/lost IUCD thread 23.8%. In 22.5% (9) of cases referred as missing/lost IUCD, the threads were visible on inspection of the cervix during speculum examination 21.4% (36) of the referred patients had routine removal by simple traction, while the retrieval hook was successfully used in 75% of the cases, only 3 patients (1.7%) required removal under general anaesthesia. A proper speculum examination combined with uterine sounding and the use of the retrieval hook at the peripheral centres will greatly reduce the need for referring IUCD related cases to a tertiary centre.

Failed contraception in Nigerian women: outcome of pregnancy and subsequent contraceptive choice.

The outcome of pregnancy in 56 patients who had contraceptive failure out of the 5,431 new acceptors at the Family Planning Clinic of the Department of Obstetrics and Gynaecology, College of Medicine, University of Lagos, between 1 January 1981 and 31 December 1989, were analysed. There were 40 IUD, 6 OC, and 4 injectable failures. Three patients had had voluntary surgical contraception (VSC) and 3 used barrier methods. The mean +/- SD age and parity were 32.2 +/- 4.4 years and 4.4 +/- 1.9, respectively. There were 17 (30.1%) live births, 34 (56.6%) terminations of pregnancy and 3 (5.2%) spontaneous abortions. Two (3.0%) patients were lost to follow-up. There was neither any statistically significant difference in the outcome of pregnancy between patients with 5 or more children and less than 5 children (p greater than 0.05), nor between patients less than 31 years of age and those older. Fifty per cent of the patients who had used the IUD continued with the method. Seven patients subsequently requested VSC. None of the patients using the injectable contraceptive or barrier methods continued with the method (p greater than 0.05).

PIP: Pregnancy outcome in 56 patients who experienced contraceptive failure out of a pool of 5431 acceptors at the Family Planning Clinic of the Department of Obstetrics and Gynecology, College of Medicine, University of Lagos, Nigeria was analyzed during the period January 1981-December 1989. There were 40 IUD, 6 oral contraceptive, and 4 injectable failures. 3 patients had undergone voluntary surgical contraception (VSC) and 3 used barrier methods. The mean +or- SD age and parity were 32.2 +or- 4.4 years and 4.4 +or- 1.9, respectively. There were 17 (30.1%) live births, 34 (56.5%) pregnancy terminations, and 3 (5.2%) spontaneous abortions. 2 (3.0%) patients were lost to follow up. There was neither any statistically significant difference in the outcome of pregnancy between those patients with 5 or more children and less than 5 children (p.05), nor between patients less than 31 years old and those who were older. 50% of those who had used the IUD continued with that method; 7 patients subsequently requested VSC. None of the patients using injectables or barrier methods continued with that method (p.05).

The attitude of fertile Nigerian women to sterilization.

PIP: 250 women selected at random from outpatients of the Department of Obstetrics and Gynaecology, Lagos University Teaching Hospital, Nigeria, were interviewed about their attitudes toward female sterilization by nurses with a standard questionnaire. Factors affecting attitudes toward sterilization were multiple and results are reported as percentages. The study population excluded women with infertility, a common problem, and further differed from the general population because the women were older and more highly educated. The number of living children was 3 or more in 59%; the ideal family size was at least 5 in 48%. 48% had used some type of contraception. 87.6% had heard of female sterilization, most often from medical personnel. Factors reported as affecting attitudes included: number of living children (59.6%); age of patient (52%); experience with complications of pregnancy and labor (45.2%); other medical disorders (36%); effect on reincarnation (17.6%); sex of living children (17.2%); fear of impotence (7.2%); and religion or culture (3.2%). The average age for female sterilization is 40 in Nigeria. A more extensive study of resistance to sterilization is indicated.^ieng