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Biomedical subjects

R K Razdan

Publications and source records attributed to R K Razdan.

At least 109 records · Page 6Linked to original sources
PubMed1976

Drugs derived from cannabinoids. 1. Nitrogen analogs, benzopyranopyridines and benzopyranopyrroles.

Various nitrogen analogs of delta6a,10a-tetrahydrocannabinol were synthesized by a general procedure described in an earlier communication. Minimum effective doses (MED50's) and lethal doses (LD50's) were determined by a modified Irwin mouse screen after iv administration of compounds in PEG 200. The most potent compounds were the propargyl (5t), allyl (5m), and chloroallyl (5o-q) derivatives. Overt behavioral effects (CNS depression, static ataxia, and hypersensitivity) of 5t and Roger Adams' carbocyclic analog (III) were found to be similar in the mouse, cat, dog, and monkey. Dichloroisoproterenol prevented and reversed many of the depressant effects of both III and 5t but had no effect on the ataxia produced by these compounds. In antinociceptive tests, 5t was active in the phenylquinone and Eddy hot-plate tests but was inactive in the tail-flick test.

Animals↗
PubMed1976

Drugs derived from cannabinoids. 2. Basic esters of nitrogen and carbocyclic analogs.

Various basic esters of nitrogen (2) and carbocyclic (3 and 4) analogs of cannabinoids were synthesized using dicyclohexylcarbodiimide in methylene chloride. The compounds in the three series werw studied in selected pharmacological tests in mice, rats, dogs, and cats. It was shown that making the basic ester from the phenol retains biological activity and can lead to a greater selectivity of action, particularly the antinociceptive activity. The most interesting esters were 5, 6, 10, and 14 in the nitrogen analogs series and 19 and 20 in the carbocyclic series. Compound 5 was more potent than codeine in the writhing, hot-plate, and tail-flick tests and is at present undergoing clinical testing. Compound 20 was very potent in the mouse audiogenic seizure test and is of interest as an anticovulsant agent.

Acoustic Stimulation↗
PubMed1976

Drugs derived from cannabinoids. 3. Sulfur analogs, thiopyranobenzopyrans and thienobenzopyrans.

Sulfur analogs of cannabinoids corresponding to DMHP (1) were prepared utilizing the Pechmann condensation between the appropriate keto ester and (5-(1,2-dimethylheptyl)resorcinol, followed by Grignard reaction. Compounds of various structural types (2-6), which had different ring size and position of the sulfur atom substituted in the alicyclic ring, were found to be active CNS agents in pharmacological tests in mice, rats, and dogs. They showed profiles qualitatively similar to those of the nitrogen and carbocyclic analogs. Basic esters of the most interesting parent phenols 2 and 4 were also prepared and tested.

Aggression↗
PubMed1976

Drugs derived from cannabinoids. 4. Effect of alkyl substitution in sulfur and carbocyclic analogs.

Various CNS-active cannabinoids in which the alicyclic ring was thiopheno, cyclopenteno, or cyclohexeno with the alkyl substituent in various positions (structural types 1-6) were synthesized by procedures described previously. These compounds were compared in selected pharmacological tests in mice, rats, dogs, and cats. The results suggested that methyl substitution in the close proximity of the phenolic hydroxyl group strongly influenced the activity of some cannabinoids, particularly of those which had a planar five-membered alicyclic ring rather than a six-membered ring.

Acoustic Stimulation↗
PubMed1976

Drugs derived from cannabinoids. 6. Synthesis of cyclic analogues of dimethylheptylpyran.

Two cyclic analogues 8 and 9 of dimethylheptylpyran (DMHP, 1) were synthesized by the Pechmann condensation of the resorcinol 4 with ethyl 4-methyl-2-cyclohexanone-1-carboxylate followed by Grignard addition with MeMgI. In selected pharmacological tests both analogues 8 and 9 were considered inactive compared to DMHP as CNS and cardiovascular agents.

Animals↗
PubMed1976

Hashish. Unsaturated side-chain analogues of delta8-tetrahydrocannabinol with potent biological activity.

Two delta8-THC derivatives, 4a and 4b, with functionalized side chains were synthesized. Treatment of (+)-trans-p-mentha-2,8-dien-1-ol with the resorcinal 2b followed by removal of the dithiol group with HgO--BF3-Et2O gave the aldehyde 3b. A Wittig reaction of dimethyl (2-oxoheptyl)phosphate with 3b furnished 4a, which was reduced to 4b. Compounds 4a and 4b showed potent cannabinoid-like activity in mice.

Animals↗
PubMed1975

Hashish. Importance of the phenolic hydroxyl group in tetrahydrocannabinols.

Optically active delta-3- and delta-8-tetrahydrocannabinols (THC's), cannabidiol and racemic delta-9-cis-THC, and their corresponding analogs (1b yields 4b) in which the positions of the phenolic hydroxyl group and the n-C5 side chain have been interchanged are compared in selected pharmacological tests in mice. the results indicate that the phenolic hydroxyl group in the 1 position in THC's is very important for eliciting activity and that cannabidiol and delta-9-cis-THC possess weak CNS depressant properties.

Animals↗
PubMed1972

Water-soluble derivatives of 1 -tetrahydrocannabinol.

Delta1-Tetrahydrocannabinol, which is resinous and insoluble in water and therefore difficult to study pharmacologically, can be converted to a watersoluble derivative without loss of its biological activity. This has been achieved by preparing esters bearing a nitrogen moiety with the use of carbodiimide as the condensing agent. The availability of such water-soluble derivatives will allow the evaluation of Delta1-tetrahydrocannabinol in self-administration studies in monkeys for its addiction liability potential in man. This technique of water solubilization is also applicable to other compounds of chemical and biological significance.

Amphetamine↗