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Biomedical subjects

N P Plotnikoff

Publications and source records attributed to N P Plotnikoff.

At least 37 records · Page 2Linked to original sources

Enkephalins as immunomodulators.

The protective effects of methionine enkephalin as well as leucine enkephalin were studied in BDF1 mice inoculated with 1 X 10(4) and 1 X 10(2) cells of L1210 murine leukemia. Significant increases in number of survivors were observed in mice treated with enkephalins. Methionine enkephalin in the presence of PHA was found to stimulate lymphocyte blastogenesis at concentrations of 1 mg/ml to 10(-8) mg/ml. In the case of leucine enkephalin, concentrations of 1 mg/ml to 10(-10) mg/ml stimulated blastogenesis. Stimulation of blastogenesis was seen at PHA dilutions of 1:100, 1:250, 1:750, with both methionine enkephalin and leucine enkephalin. The results are discussed in terms of immunomodulation. It is proposed that endogenous enkephalins play a neuroendocrine role between the central nervous system and the immune system and are direct immunostimulants.

Animals↗

Study of the structural requirements for dopa potentiation and oxotremorine antagonism by L-prolyl-L-leucylglycinamide.

A number of analogs of the tripeptide L-prolyly-L-leucylglycinamide (1) were synthesized and evaluated in the Dopa potentiation and oxotremorine antagonism tests. The replacement of the glycinamide residue with either the glycine methylamide, glycine, aminoacetonitrile, amino-2-propanone, semicarbazide, or beta-alaninamide residues resulted in a loss of activity in both tests. A 1:1 mixture of L-prolyl-L-leucyl-(-)-thiazolidine-2-carboxamide (8) and L-prolyl-L-leucyl-(+)-thiazolidine-2-carboxamide (9) showed marked activity in the Dopa potentiation test but was unable to antagonize the tremors induced by oxotremorine. L-Prolyl-L-leucyl-L-prolinamide (11), on the other hand, was active in the oxotremorine antagonism test but inactive in the Dopa potentiation test. The replacement of the pyrrolidine ring of 1 with either a thiazolidine or cyclopentane ring system caused a loss of activity. The cyclopentanecarboxylic acid analogue 13, however, was found to have moderate activity in the serotonin potentiation test.

Aggression↗

CNS and pituitary effects of hypothalamic peptides and MSH.

The first part of this essay discussed the CNS effects of the pituitary peptide MSH. These investigations anticipated studies of the CNS effects of peptides found in the hypothalamus which were discussed in the second part of the essay. Some of the endocrine actions of the hypothalamic peptides upon the release of pituitary hormones were discussed in the last part of the essay. Together, the CNS and pituitary effects of hypothalamic peptides and MSH provide intriguing examples of areas of investigation which can be expected to be greatly expanded in the future.

Adrenocorticotropic Hormone↗

Possible association of increased rat behavioral effects and increased striatal dopamine and norepinephrine levels during the DOPA-potentiation test.

Previous reports have indicated that alpha-MSH release inhibiting hormone (MIF-1) increased the behavior occurring as a result of the dihydroxyphenylalanine (DOPA) potentiation test [3,7]. This study was undertaken to see whether dopamine (DA) or norepinephrine (NE) levels likewise increased in the test animals. The DOPA potentiation test was performed as follows: 2-4 hr before behavior measurement, 40 mg/kg of the monoamine oxidase inhibitor pargyline HCl was given orally. Two hr later this was followed by the intraperitoneal (IP) injection of MIF-1 at doses of 0.1, 0.3 or 1.0 mg/kg. Behavioral measurement was begun after the IP injection of 200 mg/kg of dl-DOPA 1-2 hr after the MIF-1. The parameters included social interaction, aggressiveness, fighting, ataxia, jumping, defecation, urination and salivation. The animals were beheaded while the behavior was still increased and the striatal area removed, placed in aluminum foil, and kept at -50 degrees C until assayed. In general, especially among the younger animals, a significant correlation (p=0.05 to p=0.01) was found between the increased behavioral responses to MIF-I and the rise in DA. Because of a few exceptions to this correlation the possibility is suggested that MIF-I might also affect behavior by acting directly on the postsynaptic membrane thus bypassing any change in NE or DA which is known to increase cycli AMP in the striatum.

Animals↗

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↗

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↗

Antidepressant and anticonvulsant activity of 1-(5-phenyl-4-oxazolin-2-yl)-4-substituted piperazines.

1-(5-Phenyl-4-oxo-2-oxazolin-2-yl)-4-substituted cinnamoylpiperazines and 1-(5-phenyl-4-oxo-2-oxazolin-2-yl)-4-carbamoylpiperazine and derivatives were synthesized and evaluated for antidepressant activity in the mouse Dopa potentiation test. 1-(5-Phenyl-4-oxo-2-oxazolin-2-yl)-4-carbamoylpiperazine and derivatives were further evaluated for anticonvulsant activity in the audiogenic seizure test in mice.

Acoustic Stimulation↗