Habib Edery

Chemical Basis of Hashish Activity

A sample of hashish was extracted consecutively with petroleum ether, benzene, and methanol. When tested intravenously in monkeys only the petroleum-ether fraction was active. This material was further fractionated. The only active compound isolated was Δ1-tetrahydrocannabinol. Cannabinol, cannabidiol, cannabichromene, cannabigerol, and cannabicyclol when administered together with Δ1-tetrahydrocannabinol do not cause a change in the activity of the latter, under the experimental conditions used. These results provide evidence that, except for Δ1-tetrahydrocannabinol, no other major, psychotomimetically active compounds are present in hashish.

Ciliary motility in brain ventricular system and trachea of hamster

Ciliary beat frequency (CBF) in various parts of brain ventricular system, as well as in trachea of hamsters, was examined. Coronal sections of brain and tracheal rings were maintained in a thermostatically controlled perfusion chamber and CBF measured by a photoelectric system equipped with a fiber-optic probe. CBF (Hz) values of lateral ventricle, aqueduct and fourth ventricle were 27.9 +/- 4.6; 30.7 +/- 7.7 and 31.9 +/- 7.8 Hz, respectively. CBF in the third ventricle--19.8 +/- 7.1 Hz--was significantly lower than in other segments of ventricular system. CBF in choroid plexus cilia was very slow, 5-10 Hz, whereas in tracheal rings amounted to 13.7 +/- 3.1 Hz. Bovine cervical mucus and mucus stimulant reversibly inhibited CBF in brain but not in trachea. Brain cilia in contrast to those in trachea were not capable of transporting particles. In addition to demonstrating differences between tracheal and ependymal cilia, this work suggests that cilial motility plays a functional role in local mixing of cerebrospinal fluid, but does not relate to the bulk flow within the ventricular system.

6β-Hydroxy-δ1-Tetrahydrocannabinol Synthesis and Biological Activity

6β-Hydroxy-δ1-tetrahydrocannabinol, a metabolite of δ1-tetrahydrocannabinol has been synthesized from δ6-tetrahydrocannabinol. It shows high tetrahydrocannabinol-type activity in rhesus monkeys. The implications of this funding are discussed.

Passage of 2-hydroxyiminomethyl-N-methylpyridinium methanesulfonate to the fetus and cerebral spaces☆

Abstract The passage of 2-hydroxyiminomethyl- N -methylpyridinium methanesulfonate (P2S) to the perfused cerebral spaces of pregnant does and to their fetuses has been studied. The oxime did not penetrate into the fetus after intravenous injection of 30 mg/kg though it did after 60 mg/kg or continuous slow infusion of 2.5 mg/kg/min during 45 minutes. In all cases P2S was found in the perfusate of cerebral spaces. In animals intoxicated with tetraethyl pyrophosphate, the maternal blood cholinesterase was rapidly reactivated after injection of 30 mg/kg of P2S, but both brain and blood cholinesterase activity of the fetuses stayed reduced. Administration of 60 mg/kg reactivated the enzyme also in fetuses. It is suggested that in cases of organophosphate poisoning in pregnant females, high doses of P2S should be administered in order to reach the fetus. Continuous slow infusion of the oxime appears to be the method of choice, as it also maintains a satisfactory constant plasma level.

Release of prostaglandins mediating the potentiation of bradykinin by BPF and chymotrypsin in rat isolated ileum

following data: (1) kininogen and kinin modifications in spontaneous (SICUTERI et al. [5, 7]) and experimental (KIMURA et al. [3]) myocardial infarction; (2) lowering of prekallikrein levels in plasma in spontaneous infarction (SlCtrrERI et al. [8]); (3) relief of pain sensation and improvement of shock conditions by administration of the protease inhibitor Trasylol (SOTGIU and ARTUSO [4]) and of steroid and non-steroid anti-inflammatory agents. The suprising fact that carditis arises from myocardial infarction could be related to the high content in enzymes, mast cells, macrophages and lysosomes and the peculiar metabolic dynamics of the tissue performing continuous work. The question remains open whether inflammation is primary, triggered first by acute isehaemia and then followed by a thrombus or if the thrombotic coronary occlusion is followed by ischaemia and phlogosis. References [1] H. GESSA and W.H. STENBERC, Arch. Int. Med. 64, 249 (1939). [2] H.R. HALLSTROM, Perspect. Biol. Med. 16, 4277 (1973). [3] E. KIMURA et al., Am. Heart J. 85, 647 (1973). [4] G. SOTGIU and O. ARTUSO, Ma. Cardiovasc. 6, 1283 (1965). [5] F. SICUTERI et al., Physiopathological Aspects of Bradykinin and its Precursor p. 53, (Ed. F. Sicuteri; CEPI, Roma (1963). [6] F. SIctYrERI et al., Mal. Cardiovasc. 5, 3 (1964). [7] F. SICUTERI et al., Mal. Cardiovasc. 8, 343 (1967). [8] F. SlCtrrERI et al., Vasopeptides: Chemistry, Pharmacology and Pathophysiology, p. 448, eds. N. Back and F. Sicuteri, Plenum Press, N. Y. (1972).

Beneficial effects of alcohol in dumping syndrome and its relation to plasma kinins

Two aminopeptidases from human liver homogenates were partially purified and characterized by subcellular fractionation, chromatographic procedures and susceptibility to inhibitors. The first enzyme is a chloride-dependent aminopeptidase able to hydrolyze lysine and arginine flnaphthylamides (NA), showing no detectable activity on neutral amino-acyl NA. This enzyme is present in the soluble fraction (83%); it is inhibited 68% by 5 mM Co2+, 90% by 5