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Biomedical subjects

C F Barfknecht

Publications and source records attributed to C F Barfknecht.

At least 55 records · Page 3Linked to original sources
PubMed1978

Aminotetralin analogs of methoxamine as potential hypertensive agents.

Cardiovascular effects of methoxamine and some aminotetralin derivatives (5,8-ADT, DR-31 and DR-17) were studied after systemic intravenous or intraarterial injection into different perfused vascular beds in anesthetized dogs. Intravenous administration of the compounds produced dose-related prolonged increases in blood pressure, which were antagonized by phentolamine. After intro-arterial injection into the perfused hindlimb, mesenteric artery or the saphenous vein, all compounds produced dose-dependent increases in perfusion pressure indicative of vasoconstriction. Phentolamine antagonized these effects. It was demonstrated that desipramine significantly reduced the vasoconstricting actions of intra-arterially injected tyramine in the hindlimb, but did not alter the responses induced by methoxamine and the aminotetralin derivatives. The data indicate that these compounds elicit peripheral vasoconstriction in the dog, through a direct action on the alpha adrenergic receptors.

Animals↗
PubMed1976

NMR study of amphetamines using europium shift reagents.

Amphetamine and certain of its methoxylated derivatives show a high degree of interaction with NMR shift reagents of the type tris (1,1,1,2,2,3,3-heptafluoro-7,7-dimethyl-4,6-octanedione)europium(III). The shifts are not accompanied by appreciable line broadening, and both the aliphatic and aromatic protons can be resolved. The strong interaction between amine and shift reagent diminishes rapidly as the amine function is alkylated. For derivatives containing ortho-methoxyl groups, a weaker interaction with this functionality also becomes evident as the amine is alkylated. The stereospecificity of the shifting process was investigated by employing tris[3-(trifluoroacetyl)-d-camphorato]europium(III), a chiral shift reagent, with stereochemically pure enantiomers and known enantiomeric mixtures. Although certain (R)-enantiomers showed greater downfield C-methyl groups shifts, these shift differences from the corresponding (S)-enantiomers were small and not well resolved.

Amphetamines↗
PubMed1976

The antagonism of nicotine-induced cardiovascular responses by DMAE and DEO analogs.

A series of quaternary ammonium compounds cinsisting of 4, 4'-bis-[N-(2, 2-diethoxyethyl)-N, N-dimethylammonioacetyl]-biphenyl dibromide (DMAE) and 4, 4'-bis-[N, N-di(2-ethoxyethyl)-N-methylammonioacetyl]-biphenyl dibromide (DEO) analogs was investigated for selective nicotine antagonism. Each series of compounds contained the monophenyl (MPh.DMAE, MPh.DEO); biphenyl (DMAE, DEO); terphenyl (TPh,DMAE, TPh.DEO); half-molecule (1/2DMAE, 1/2DEO); p-phenyl half-molecule (p-Ph.-1/2DMAE, p-Ph.-1/2DEO) and biphenyl half-molecule (p-BPh.-1/2DMAE, p-BPh.-1/2DEO) analogs. Studies were conducted on isolated spontaneously beating guinea pig atria and anesthetized dogs. Relative potencies of the DMAE and DEO series to antagonize the nicotine (20 mug/ml) induced positive chronotropic effect of the guinea pig atria were determined as follows: DMAE (1.0); TPh.DMAE (0.82); P-Ph.1/2DMAE (0.59); DEO (0.54); MPh.DMAE (0.27); TPh.DEO (0.26); MPh.DEO (0.18); p-Ph.-1/2DEO (0.16); 1/2DMAE (0.03); 1/2DEO (0.02); p-BPh.-1/2DMAE (less than 0.01); p-BPh.-1/2DEO (less than 0.01) and C-6 (0.85). The I50 to antagonize nicotine induced responses by DMAE was 0.13 muM (0.10 mu/ml). Several of the above analogs were studied in the dog and their ability to antagonize nicotine (100 mug/kg) induced positive chronotropic effects were compared with their ability to inhibit transmission through the stellate or the superior cervical ganglia. The I50 doses of the drugs antagonizing nicotine, impairing superior cervical ganglionic transmission and the corresponding fold shifts in the dose--response curves follow: DMAE (120 mug/kg, 3.0 mg/kg, 25); TPh.DMAE (40 mug/kg, 1.10 mg/kg, 30), DEO (45 mug/kg, 1.30 mg/kg, 25) and C-6 (140 mug/kg, 0.42 mg/kg, 0.42 mg/kg, 3.0). These findings are suggestive of the hypothesis that receptors normally activated by endogenously released ACh in the stellate or superior cervical ganglia of the dog may be dissociated from those receptors activated by nicotine which results in an increase in blood pressure or heart rate. Clinical implications are that TPh.DMAE as well as other DMAE analogs may pose less of a problem with hypotension than hexamethonium as a nicotine antagonist.

Animals↗
PubMed1976

Ergoline congeners as potential inhibitors of prolactin release. 2.

In our attempts to elucidate the prolactin release inhibiting pharmacophore within the ergoline structure, we have prepared one indolealkylamine and several 2-aminotetralin derivatives. These congeners have been evaluated for inhibition of prolactin release in vivo. One congener, 5,8-dihydroxy-2-dimethylaminotetralin, and the drug M-7 significantly inhibited prolactin secretion.

Animals↗
PubMed1975

Correlation of psychotomimetic activity of phenethylamines and amphetamines with 1-octanol-water partition coefficients.

In an attempt to relate the hallucinogenic potencies in man of some biologically important amphetamines and phenethylamines, the 1-octanol-water partition coefficients for 11 amphetamines were determined. Using these values and published Hansch pi constants, the log P for 17 additional amines was estimated. It was found that lipophilicity, as measured by the log of the partition coefficient, may be a significant determinant of the level of hallucinogenic potency. The study also suggests that an ideal log P value for psychotomimetric activity in man may be from 2.89 to 3.72.

Amphetamines↗
PubMed1975

Nonclassical nicotine antagonists.

A series of "nonclassical" nicotine antagonists was synthesized and compared to the "classical" nicotine antagonist, hexamethonium, by means of the isolated guinea pig atria preparation. 2 was found to be the most potent, followed by hexamethonium and the other antagonists. With the exception of 5, the bisquaternary compounds 1-3 and 7-9 were found to be more potent than the monoquaternary compounds 4, 6, and 10-12. Within a series of compounds (1-6 or 7-12), those compounds possessing two phenyl rings proved to be more potent than those possessing one or three phenyl rings. These and other aspects of the structure-activity relationship of this class of compounds are discussed.

Animals↗