Effects of idazoxan on 5-hydroxytryptamine-mediated behaviour in the mouse and rat.

The α(2)-adrenoceptor antagonists idazoxan and RX811059 induced reciprocal forepaw treading, a component of the 5-HT-behavioural syndrome in rats. This response is independent of 'non-α(2)-adrenoceptor idazoxan binding sites' (NAIBS) at which RX811059 is inactive. Idazoxan pre-treatment, in rats, enhanced forepaw treading, head weaving and tremor induced by the 5-HT agonist 5-methoxy-N,N dimethyltryptamine (5-MeODMT), increased head twitches (but decreased hindlimb abduction) induced by the 5-HT releaser p- chloroamphetamine (pCA), but did not clearly alter head twitches induced by the 5-HT precursor L-5-hydroxytryptophan in mice.

Specific α2-adrenoreceptor antagonists induce behavioural activation in the rat.

The behavioural effects of the specific and selective α(2)-adrenoreceptor antagonists, idazoxan, efaroxan and RX811059, have been investigated in the rat. All three drugs induced periods of behavioural activation characterized by increased locomotion and exploration (rearing and hole dipping). However, these effects were only apparent in animals which were fully habituated to their environments and thus displayed low baseline activity.

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.

Antihypertensive thiadiazoles. 1. Synthesis of some 2-aryl-5-hydrazino-1,3,4-thiadiazoles with vasodilator activity.

Some 2-aryl-5-hydrazino-1,3,4-thiadiazoles have been synthesized and screened for antihypertensive activity. In general, compounds with a 2-substituted phenyl ring had higher activity than their 3- or 4-substituted counterparts or those containing heteroaryl groups. The 2-methylphenyl and 2-ethylphenyl derivatives 7 and 18 were the most potent members of the series.

Alpha 1- and alpha 2-adrenoreceptor antagonists differentially influence locomotor and stereotyped behaviour induced by d-amphetamine and apomorphine in the rat.

The importance of dopamine (DA) in mediating locomotor, exploratory and stereotyped behaviour in rodents is well established. Evidence also indicates a modulatory role for noradrenaline (NA) although, due to nonspecificity. of previously available agents, a precise role remains undefined.