Association between culture and the preference for, and perceptions of, 11 routes of medicine administration: A survey in 21 countries and regions.

Medicines can be taken by various routes of administration. These can impact the effects and perceptions of medicines. The literature about individuals' preferences for and perceptions of the different routes of administration is sparse, but indicates a potential influence of culture. Our aim was to determine: (i) any association between one's culture and one's preferred route of medicine administration and (ii) individual perceptions of pain, efficacy, speed of action and acceptability when medicines are swallowed or placed in the mouth, under the tongue, in the nose, eye, ear, lungs, rectum, vagina, on the skin, or areinjected. A cross-sectional, questionnaire-based survey of adults was conducted in 21 countries and regions of the world, namely, Tunisia, Ghana, Nigeria, Turkey, Ethiopia, Lebanon, Malta, Brazil, Great Britain, United States, India, Serbia, Romania, Portugal, France, Netherlands, Japan, South Korea, Hong Kong, mainland China and Estonia, using the Inglehart-Welzel cultural map to ensure coverage across all cultures. Participants scored the pain/discomfort, efficacy, speed of onset and acceptability of the different routes of medicine administration and stated their preferred route. Demographic information was collected. A total of 4435 participants took part in the survey. Overall, the oral route was the most preferred route, followed by injection, while the rectal route was the least preferred. While the oral route was the most preferred in all cultures, the percentage of participants selecting this route varied, from 98% in Protestant Europe to 50% in the African-Islamic culture. A multinomial logistic regression model revealed a number of predictors for the preferred route. Injections were favoured in the Baltic, South Asia, Latin America and African-Islamic cultures while dermal administration was favoured in Catholic Europe, Baltic and Latin America cultures. A marked association was found between culture and the preference for, and perceptions of the different routes by which medicines are taken. This applied to even the least favoured routes (vaginal and rectal). Only women were asked about the vaginal route, and our data shows that the vaginal route was slightly more popular than the rectal one.

Inhibitory effect of 3-carboethoxypyridine and 3-carbobutoxypyridine on isolated rat uterus.

3-Carbomethoxypyridine (CMP) was isolated and characterized from the leaves of Pyrenacantha staudtii Hutch and Dalz, family Icacinaceae, in our earlier study and was found to possess an inhibitory activity on the isolated rat uterus. In order to study the structure - activity relationship, derivatives of CMP were obtained synthetically, purified and characterized by spectroscopic techniques such as infra red spectroscopy (IR), nuclear magnetic resonance (1H- and 13C-NMR) and mass spectrometry (MS). The synthesized compounds were subjected to pharmacological testing using isolated rat uterine preparation in oestrus suspended in an organ bath containing De Jalon physiological salt solution (PSS). The force of contraction was recorded via an isometric transducer connected to an Ugo Basile recorder. The effects of these two compounds were compared with salbutamol as a positive control. 3-Carboethoxypyridine (ECP) demonstrated very significant (p < 0.005) inhibitory activity on the uterus with a total elimination of the spontaneous contractility at a dose of 0.4 mg/mL. Carbobutoxypyridine (BCP) also demonstrated a marked reduction of oxytocin-induced contractions and elimination of spontaneous activity. The study lends support to the potential use of these agents as tocolytics.

Synthesis and pharmacological evaluation of carboxamides.

Some carboxamide derivatives with potential anti-inflammatory and analgesic properties were synthesized from the reaction of phthalimido alkyl acids with benzylamine at room temperature. All the compounds synthesized were unequivocally confirmed by means of Infrared, Nuclear Magnetic Resonance (1H and 13C), Mass spectrophotometer, and elemental analyses. The carboxamides were evaluated pharmacologically for their in vivo anti-inflammatory and analgesic activities by carrageenan-induced rat paw oedema and acetic acid-induced writhing test respectively. All the investigated compounds exhibited significant anti-inflammatory activity in the range of 45 to 70% in comparison to control. They showed promising analgesic activity at the dose used. 3-Benzamido-propionic acid -2-(N-benzyl)-carboxamide (4) exhibited the highest anti-inflammatory and analgesic activities and the effects were dose-dependent.

Anti-inflammatory and gastroprotective properties of some chalcones.

The synthesis of 1,3-diaryl propen-1-ones (chalcones) by the Claisen-Schmidt condensation between acetophenones and benzaldehydes in potassium hydroxide/methanol medium at room temperature yielded: 1-(4-nitrophenyl)-3-(2,4,6-trimethoxyphenyl)propen-1-one (3a), 1-(4-nitrophenyl)-3-(3-bromophenyl)propen-1one (3b), 1-(4-methoxyphenyl)-3-(3-bromophenyl)propen-1-one (3c), 1-(4-methoxyphenyl)-3-(2,4,6-trimethoxyphenyl)propen-1-one (3d), 1-(2,4-dihydroxyphenyl)-3-(phenyl)propen-1-one (3e), 1-(4-nitrophenyl)-3-(4-chlorophenyl)propen-1-one (3f) which were evaluated for anti-inflammatory activity at doses of 20, 40 and 80mg/kg. The compounds were found to be effective inhibitors of carrageenan-induced rat paw edema in Wistar rats and this activity was dose dependent and increased between the third and fourth hour. The gastroprotective activity of the compounds was investigated (using 200 mg/kg acetylsalicylic acid-induced ulceration) in Wistar rats at a single dose of 100 mg/kg for all the compounds synthesized and compound 3d had significant activity (p<0.001) comparable to cimetidine. The compounds were found to have anti-inflammatory and anti-ulcer activities at the doses employed.

Ring opening of 1-phthaloylimido-[4-(2-methoxyphenyl) piperazin-1-yl]alkyl derivatives: synthesis, analgesic and anti-inflammatory properties of products.

Phthaloylimidoalkyl derivatives (1a, 1b) were treated with isopropylamine to give 3-benzamido-1-(4-(2-methoxyphenyl)piperazin-1-yl)]propyl-2-isopropyl carboxamide (3a) and 4-benzamido-1-(4-(2-methoxyphenyl)piperazin-1-yl)butyl-2-isopropyl carboxamide (3b). The compounds were unequivocally characterized by IR, NMR and MS spectra and elemental analysis. Carrageenan-induced rat paw assay was used to screen 3a and 3b for anti-inflammatory activity. 3b significantly (p <0.001) inhibited the inflammation caused by carrageenan after 3 h compared to 3a and indomethacin. Mouse writhing assay was performed to evaluate 3a and 3b. It revealed that 3b (10 mg/kg) produced 71% inhibition when compared to 3a (40 mg/kg) and acetylsalicylic acid (100 mg/kg). The results show that the length of the alkyl chain that separates the terminal nitrogen atom from the phthalic acid moiety also affects the activity of 3a and 3b in a dose dependent manner.

Isolation and characterization of 3-carbomethoxypyridine from the leaves of Pyrenacantha staudtii Hutch and Dalz (Icacinaceae).

Pyrenacantha staudtii is a medicinal plant used widely in the West African sub-region particularly in Nigeria for the treatment of threatened abortion and dysmenorrhea. This study reports for the first time the chemical isolation and characterization of 3-carbomethoxypyridine from one of the active fractions of the methanolic extract of Pyrenacantha staudtii leaves. The crude methanolic extract was subjected to accelerated gradient chromatography (AGC) to give various fractions. One of the active fractions was further subjected to a reversed phase lobar column chromatography to give the alkaloidal compound using methanol : water as solvent system. The structure was unequivocally determined by physical, chemical and spectral techniques.

Synthesis and pharmacological evaluation of 2-hydroxymethylbenzamides as anti-inflammatory and analgesic agents.

The ring opening of some phthalimide derivatives with sodium borohydride in methanol/water (6:1) afforded the corresponding 2-hydroxymethylbenzamides irrespective of the substituents. The most active members of the series evaluated for anti-inflammatory and analgesic activities were 2-hydroxymethyl-N-[4-(2-methoxyphenyl)-piperazin-1-yl]-ethylbenzamide (3d) and 2-hydroxymethyl-N-[4-(2-methoxyphenyl)-piperazin-1-yl]-propylbenzamide (3e), respectively.

Studies on quinazolines. 11. Intramolecular imidate-amide rearrangement of 2-substituted 4-(omega-chloroalkoxy)quinazoline derivatives. 1,3 -O --> N shift of chloroalkyl groups via cyclic 1,3-azaoxonium intermediates.

The omega-chloroalkylation of 2-substituted quinazolin-4(3H)-one derivatives 1 and 2 with Br-(CH(2))(n)-Cl (n = 2-4) and the intramolecular imidate-amide rearrangement of the alkylated products are described. At room temperature, the 2-phenyl substituent promoted O-alkylation, whereas the less steric 2-benzyl group led to a higher ratio of N-alkylation. The investigation of the O-alkylated products, 4-omega-chloroalkoxyquinazolines, revealed that the migration of omega-chloroethyl and omega-chloropropyl groups from oxygen to nitrogen should be intramolecular via five- and six-membered cyclic 1,3-azaoxonium intermediates, respectively. Competition between rearrangement and nucleophilic substitution results in the formation of 7a,b and 8a,b from the nucleophilic substitution of 4a,b and 6a,b, respectively.