Early microdose drug studies in human volunteers can minimise animal testing: Proceedings of a workshop organised by Volunteers in Research and Testing.

Testing the safety and efficacy of a successful human medicine involves many laboratory animals, which can sometimes be subjected to considerable suffering and distress. Also, it is necessary to extrapolate from the test species to humans. UK and European legislation requires that Replacement, Reduction and Refinement of animal procedures (the Three Rs) are implemented wherever possible.

Bi-, Tri-, and Tetranuclear Metallomacrocycles Constructed by Metal-Directed Reactions Involving Resorcinol or Hydroquinone or by Addition of Octahedral Metal Centers to Tetrahexylcalix[4]resorcinarene: X-ray Crystal Structure of syn,syn-[Mo{HB(3,5-Me(2)C(3)HN(2))(3)}(NO)(1,4-O(2)C(6)H(4))](3).

The reaction between [Mo(NO)(Tp)I(2)] [Tp(-) = hydrotris(pyrazol-1-yl)borate] and tetrahexylcalix[4]resorcinarene (resH(8)) affords a mixture of metalated macrocycles from which [{Mo(NO)(Tp)}(2)(resH(4))], [{Mo(NO)(Tp)}(3)(resH(2))], and [{Mo(NO)(Tp)}(4)(res)] can be isolated. In the solid state the tetrametalated compound can act as a host for CH(2)Cl(2) which forms a weak hydrogen bond to the oxygen of a coordinated nitric oxide: H.O1 2.

Comparison of the effects of efaroxan and glibenclamide on plasma glucose and insulin levels in rats.

The effect of efaroxan (1 and 5 mg/kg p.o.; a selective alpha 2-adrenoceptor antagonist) was compared to glibenclamide (1 and 5 mg/kg p.

Selectivity profile of the alpha 2-adrenoceptor antagonist efaroxan in relation to plasma glucose and insulin levels in the rat.

The effects of efaroxan (RX 821037A; 2-[2-(2-ethyl-2,3-dihydrobenzofuranyl)]-2-imidazoline HCl) at alpha 1- and alpha 2-adrenoceptors were investigated in isolated tissues, pithed rats and conscious rats. In isolated tissues, efaroxan competitively antagonised the inhibitory effects of p-aminoclonidine in the electrically stimulated (0.1 Hz) rat vas deferens, (pA2 = 8.

Antihypertensive thiadiazoles. 2. Vasodilator activity of some 2-aryl-5-guanidino-1,3,4-thiadiazoles.

Some 2-aryl-5-guanidino-(or N-substituted guanidino)-1,3,4-thiadiazoles and closely related analogues were found to lower blood pressure in metacorticoid (DOCA) hypertensive rats. In the unsubstituted guanidines that exhibited low toxicity, optimum activity resulted when the aryl group was a 2-methylphenyl ring (11). Modifications to the guanidine group did not increase antihypertensive activity, but, in the 2-methylphenyl series, the N-n-butyl- and N-(2-methoxyethyl)guanidines (63 and 78) and the related iminoimidazolidine 93 were of comparable activity to that of the unsubstituted guanidine 11.