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Biomedical subjects

R Mechoulam

Publications and source records attributed to R Mechoulam.

At least 145 records · Page 8Linked to original sources
PubMed1979

Structure--activity relationships of pyrrole amidine antiviral antibiotics. 1. Modifications of the alkylamidine side chain.

Representatives of three types of side-chain analogues of distamycin A (1) were synthesized. These were tested for cytotoxicity, inhibition of herpes simplex virus (HSV) replication in cultured cells, effects on the synthesis of HSV DNA in isolated nuclei in vitro, as well as on DNA synthesis by purified HSV DNA polymerase. Distamycin A was the most active compound in all three antiviral tests, as well as the most toxic. However, several compounds, in particular the aromatic analogues 15 and 16, showed no toxicity under the experimental conditions used but were still very active in the three antiviral tests.

Animals↗
PubMed1978

Toward drugs derived from cannabis.

Recent work aimed at the introduction of natural and synthetic cannabinoids as drugs is reviewed. Delta1-Tetrahydrocannabinol (delta1-THC) is mainly investigated as a potential drug against glaucoma and asthma, and as an antiemetic agent in cancer chemotherapy. Cannabidiol is being tried in the clinic against epilepsy and as a hypnotic. Numerous synthetic cannabinoids are currently being investigated as analgetics and as sedative-relaxants.

Analgesics↗
PubMed1975

Anticonvulsant activity of four oxygenated cannabidiol derivatives.

A pharmacological comparison between cannabidiol (CBD) and four CBD derivatives, namely CBD-aldehyde-diacetate (I), 6-oxo-CBD-diacetate (II), 6-hydroxy-CBD-tri-acetate (III), and 9-hydroxy-CBD-triacetate (IV) was carried out in mice. Protection against maximal electroshock convulsions, potentiation of pentobarbital sleeping-time and reduction of spontaneous motor activity were the effects measured. All 5 compounds were equally potent in potentiating barbiturate sleeping time at doses ranging from 6.25 to 100 mg/kg. At 12.5 and 25 mg/kg only CBD and IV were able to decrease significantly the spontaneous motor activity. CBD, II, III and IV were also active in protecting mice against electroconvulsive shock at doses of 100-200 mg/kg, although at the larger dose CBD and compound II were the most efficient. Compound I was toxic, killing about half of the animals within 24 h after injection.

Animals↗
PubMed1975

Cannabinoids: influence on neurotransmitter uptake in rat brain synaptosomes.

We have examined the effect of Delta1-tetrahydrocannabinol (delat1-THC) and 12 of its derivatives on the uptake of 3H-labeled norepinephrine (NE), dopamine (DA), serotonin (5-HT) gamma-aminobutyric acid (GABA) into synaptosomes in homogenates of various regions of rat brain. Delta1-THC inhibits the accumulation of NE and 5-HT into hypothalamic preparations and DA into the corpus striatum with Ki values of about 12 to 25 muM while GABA uptake into cerebral cortical preparations is inhibited less (Ki = 140 muM). The affinities of delta6-THC, 7-hydroxy-delta1-THC, 7-hydroxy-delta6-THC and cannabidiol for 5-HT, NE and GABA transports are similar to values for delta1-THC, while cannabigerol, cannabinol and delta6-THC-7-oic acid have substantially less affinity. Thus, hydroxylation of C-7 in delta6-THC does not alter inhibitory potency, but its oxidation to an acid and aromatization of ring A greatly reduce affinity. The hydroxyl at C-3(1) of ring C is critical for inhibition of NE, 5-HT and GABA uptake, since its acetylation or methylation abolishes activity. Inhibition of NE, DA, 5-HT and GABA uptake by all cannabinoids examined is noncompetitive. Only about 1% of delta1-THC and delta6-THC and 5% of cannabidiol are fully soluble under our experimental conditions.

Acetylation↗