Antagonism of Central Vasomotor Effects of Lysergic Acid Diethylamide (Lsd-25) by Morphine

Abstract

Lysergic acid diethylamide and morphine have been shown to antagonise certain actions of each other. LSD-25 antagonises morphine induced analgesia in rats(1) and emesis in dogs (2). It also blocks the miotic action of morphine (3). On the other hand, morphine blocks LSD-25 pyrexia in rabbits (4). The present study was undertaken to investigate if morphine could antagonise the central hypotensive action of LSD-25 reported by Ginzel (5). METHODSThe results reported here were obtained in 14 adult mongrel dogs of either sex, pen tobarbitalised (30 mg/kg, i.v.), bilaterally vagotomised and artificially ventilated (50 ml/ kg, 16/min). The left common carotid artery was cannulated to record the blood pres sure with a mercury manometer on smoked paper. The drugs were administered in the left lateral cerebral ventricle (intraventricularly) through a polythene cannula implanted according to the technique of Bhargava and Tangri (6). The drugs were administered dissolved in 0.25 ml distilled water (lysergic acid diethylamide tartrate) or normal saline (morphine hydrochloride) followed by same volume of the blank fluid. Control adminis tration of 0.5 ml distilled water or normal saline adjusted to the pH of the drug were without any effect. The drug effects were assessed on the basis of alterations in the blood pressure level as well as the reflex pressor response to the bilateral carotid artery occlusion (carotid occlusion response). RESULTS A. Efect of LSD-25Intraventricular administration of graded doses of LSD-25 in a few preliminary ex periments showed that 0.3 mg of the drug produced a significant fall in blood pressure as well as a reduction in the carotid occlusion response. The effect started immediately, the peak was reached in about 14 minutes (Table 1) and average duration of the effect was 68 ± 16 minutes. The reduction in the carotid occlusion response could not always be cor related with the magnitude of hypotension. In certain cases a comparatively smaller fall of blood pressure was acccompanied with a marked reduction of the carotid occlusion res

Effects of selected opioid agonists and antagonists on DMT-and LSD-25-induced disruption of food-rewarded bar pressing behavior in the rat

“…LSD antagonizes morphineinduced analgesia in rats (Dhawan and Gupta 1959), emesis in dogs (Dhawan and Gupta 1961), and some narcotic actions of morphine (Murphree 1965). Conversely, morphine antagonizes LSD-induced pyrexia in rabbits (Dhawan 1960), and LSD-induced hypotension and carotid occlusion response in dogs (Gupta et al 1968). A search for the morphine crystal pharmacophoric pattern coordinates in other mol-ecules, consisting of the aromatic ring and remote nitrogen atom, disclosed the identical crystal structure in LSD as an important molecular similarity (Gund 1977).…”