Summary1. AQ 110 is a 3-adrenoceptor agonist which, like isoprenaline and salbutamol, acts directly on the receptors. 2 Compared with isoprenaline, AQ 110 has relatively stronger actions on bronchial and vascular smooth muscle (P2-adrenoceptors) than stimulant effects on heart muscle (ft1-adrenoceptors). The fl2-selectivity of AQ 110 is, however, much less than that of salbutamol, mainly due to the weak cardiac actions of the latter.3. At doses which were equipotent in decreasing the bronchoconstrictor effect produced by a standard dose of 5-hydroxytryptamine, AQ 110 had marginally less hypotensive action than salbutamol and considerably less than isoprenaline. 4. Although AQ 110, unlike salbutamol, possesses a catechol group it was found not to be a substrate for catechol-O-methyl transferase and this is considered to account for its significantly prolonged action, compared with isoprenaline, in vivo.
If formation and absorption of the cerebrospinal fluid (c.s.f.) occur at different sites an intervening circulation of the fluid is obligatory, and such a circulation may appreciably modify the spread of drugs introduced into the c.s.f. Nevertheless, few controlled observations have been made on this subject. The problems involved, with particular reference to spinal anaesthesia in man, were described by Maxson (1938), who also studied the movements under various conditions of red ink in an artificial spinal fluid contained in a glass model. Sachs, Wilkins & Sams (1930) compared by direct observation the movements of a marker dye introduced at various sites into the spinal subarachnoid space of anaesthetized dogs with those occurring in a glass model.The general aim of the present investigations is to study the effects of bodily activity upon the c.s.f. circulation. In this paper the movements of a marker dye in the spinal subarachnoid space of the prone horizontal anaesthetized cat have been compared with those occurring in a glass model. The effects of tilting or shaking the animal have been studied and also the effect of picrotoxin convulsions.
METHODSCats were anaesthetized by intraperitoneal injection of sodium pentobarbitone (Abbott Laboratories, 30-40 mg/kg). In each experiment a cannula of known length and volume was inserted into the dorsal spinal subarachnoid space at one of three sites. When the cannula was to be inserted at the sacral site the laminae of the three sacral vertebrae were resected and the underlying extradural fat removed. A nylon cannula (No. 1 'Portex', Portland Plastics) with two oppositely-placed holes close to its sealed tip, filled with Ringer-Locke solution and stoppered, was introduced and tied in place with its tip pointing cranially at the first sacral vertebral level. In experiments in which the cannula was to be inserted at the cervical site, after laminectomy the right eighth cervical dorsal nerve root was exposed for about 5 mm from the cord. A cannula, as before, was introduced via the nerve-root sheath and tied so that it lay transversely across the subarachnoid space. For insertion at the thoracic site, after laminectomy the cannula (No. 00 'Portex') was introduced via the right twelfth thoracic nerve-root sheath and fixed with its tip cranially directed at the eleventh thoracic vertebral level.
Summary1. The predominant effect of morphine, diamorphine, pethidine or nalorphine on the blood pressure of the anaesthetized cat or rabbit is hypotension although, occasionally, a pressor action may predominate or intervene. 2. Possible mechanisms of the depressor phases of action have been studied on cardiac and vascular preparations both in situ and in vitro. 3. While in the whole animal, catecholamine release from the adrenal medulla and histamine liberation may be implicated in the responses, the vasodilator and vascular relaxant actions of morphine and, probably, pethidine, nalorphine and diamorphine on the isolated preparations are not mediated by the liberation of known peripheral transmitters or autacoids or by interaction with their specific receptors.
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