The influence of ACEA--a selective cannabinoid CB1 receptor agonist on whole blood and platelet-poor plasma serotonin concentrations.

Through the CB1 receptor cannabinoids modulate serotonin (5-hydroxytryptamine, 5-HT) release in the central nervous system which is connected with some of their pharmacological effects, especially antidepressant activity. 5-HT has many important physiological functions also in the periphery, particularly in the circulatory system and digestive tract. 5-HT dysfunction may be involved in some diseases pathogenesis including hypertension, migraine, cardiac disorders, cerebral ischemia or peripheral vascular diseases. Cannabinoids possible influence on 5-HT release in peripheral tissues may be clinically significant. The aim of the present study was to investigate the influence of ACEA (arachidonyl-2-chloroethylamide), a selective cannabinoid CB1 receptor agonist on whole blood (WB) and platelet-poor plasma (PPP) 5-HT levels. The experiments were carried out on male and female Wistar rats. ACEA (3 mg/kg i.p.) was given alone and in combination with a selective CB1 receptor antagonist AM 251 (3 mg/kg i.p.). Concentrations of 5-HT in WB and PPP were determined by enzyme-linked immunosorbent assay (Serotonin ELISA). ACEA significantly decreased concentration of 5-HT in WB (to 61%, p < 0.02) and its effect was blocked by AM 251. ACEA also reduced of 5-HT in PPP (to 62%) however, the difference was statistically insignificant. Research results reveal that due to CB1 receptor stimulation, ACEA reduces 5-HT contents in bloodstream. This effect is probably the result of inhibition of 5-HT release from gastrointestinal tract.

Behavior of silica particles introduced into an isolated rat heart as potential drug carriers.

Silica powders consisting of small spherical particles (50-200 nm) have been obtained by the sol-gel method. A suspension of such particles in the Krebs-Hanseleit solution has been introduced into the coronary circulation of a beating perfused rat heart. The influence of the suspension on the heart muscle and the coronary vessels in the rat body has been histopathologically examined. The particles have not left the lumen of the vessels and have not caused any side effects. These observations suggest the possibility of using such silica particles as a carrier for selected drugs.

Synthesis and anxiolytic activity of 1-phenyl-2-(4-aryl-1,3,4,5-tetrahydropyrido[2,3-b][1 ,4]diazepin-2-ylidene)-ethanone.

A two-step, general synthesis of 1-phenyl-2-(4-aryl-1,3,4,5-tetrahydropyrido[2,3-b][1,4]diazepin-2-ylidene)-ethanones 3-9 is presented. This synthesis employs a condensation of 2,3-diaminopyridine with benzoylacetone followed by a basic-activated cyclization reaction with substituted benzaldehydes for final closure of the seven-membered ring. Molecular diversity is fixed by appropriate aldehydes: 2-chloro-, 4-chloro-, 2-bromo-, 4-bromo-, 4-fluoro-, 4-trifluoro- and 3-bromo-4,5-dimethoxybenzaldehyde. Compounds 4, 6, 8, 9 and 10 were examined for their anxiolytic activity. The most active was the compound with the chlorophenyl substituent i.e. 1-phenyl-2-{4-(4-chlorophenyl)-1,3,4,5-tetrahydropyrido[2,3-b][1,4]diazepin-2-ylidene}-ethanone (4).