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Biomedical subjects

J M Kitzen

Publications and source records attributed to J M Kitzen.

26 records · Page 2Linked to original sources
PubMed1983

2,3-dihydro-3-(1-pyrryl)spiro[benzofuran-2,4'-piperidine]s and 2,3-dihydro-3-(1-pyrryl)spiro[benzofuran-2,3'-pyrrolidine]s: novel antihypertensive agents.

A series of 2,3-dihydro-3-(1-pyrryl)spiro[benzofuran-2,4'-piperidine]s (IV) and 2,3-dihydro-3-(1-pyrryl)spiro[benzofuran-2,3'-pyrrolidine]s (V) was synthesized and evaluated for cardiovascular activity. The majority of the compounds displayed good antihypertensive activity in the spontaneous hypertensive rat model at 50 mg/kg po. Compounds 5 (2,3-dihydro-1'-methyl-3-(1-pyrryl)spiro[benzofuran-2,4'-piperidine] ) and 12a (2,3-dihydro-1'-ethyl-3-(1-pyrryl)-spiro[benzofuran-2,4'-piperidine] ) were selected for a more detailed cardiovascular evaluation in the renal hypertensive rat and for standard cardiovascular challenges in anesthetized dogs and the sinoaortic-deafferented dog.

Animals↗
PubMed1982

[(3-aryl-1,2-benzisoxazol-6-yl)oxy]acetic acids. A new diuretic series.

A series of [(3-aryl-1,2-benzisoxazol-6-yl)oxy]acetic acids was synthesized and tested for diuretic activity in saline-loaded mice and in conscious, water-loaded dogs. The structural requirements for good diuretic activity in both mice and dogs were found to be very specific. In summary, the compounds with the best diuretic activity (13i, 13q, and 13ff) were substituted with a 2-fluorophenyl group at the 3 position and chlorine or bromine at the 7 position. Compound 13ff, [(7-bromo-3-(2-fluorophenyl)-1,2-benzisoxazol-6-yl]oxy]acetic acid (HP 522), was found to be moderately uricosuric in chimpanzees and was selected for further development.

Animals↗
PubMed1979

The effects of two analogs of dopamine on ganglionic transmission in the sympathetic nervous system.

Two aminotetralin analogs of dopamine were studied for their effects on ganglionic transmission in the sympathetic nervous system. Nerve activity (spontaneous firing or evoked action potentials) was recorded on a preganglionic nerve (splanchnic), a mixed nerve (lumbar chain) and several postganglionic nerves (external carotid branch and renal nerve). 6,7-Dihydroxy-2-dimethylaminotetralin and 5,6-dihydroxy-2-dimethylaminotetralin were observed to markedly inhibit spontaneous firing in the renal nerve, external carotid branch and lumbar chain. Splanchnic nerve activity was unaltered, 6,7-Dihydroxy-2-dimethylaminotetralin also depressed evoked responses to submaximal stimulation in the external carotid branch and lumbar chain. These results suggest a ganglionic site of action. Since functional vasomotor activity in the isolated perfused canine forelimb in response to preganglionic nerve stimulation was unaltered, it was concluded that 6,7-dihydroxy-2-dimethylaminotetralin may depress transmission only at certain ganglionic pathways.

Animals↗
PubMed1978

Vasodilator activity of adenosine analogs.

Various adenosine analogs were evaluated as smooth muscle vasodilators. The compounds were screened ititially using a dog hindlimb preparation. Most analogs were less potent than adenosine. The three most potent compounds were tested for coronary vasodilator effects and duration of action on the isolated rabbit heart. 5'-Deoxy-5'-chloroadenosine and 5'-deoxy-5'-bromoadenosine were equipotent with adenosine but possessed a longer duration of action 2',3',5'-Trideoxy-3',5'-dichloroadenosine, an analog lacking both the 2'- and 3'-hydroxyl groups, had significant vasodilator activity.

Adenosine↗
PubMed1978

Pharmacology of 6,7-dihydroxy-2-dimethylaminotetralin (TL-99). I. Cardiovascular activity in the dog and cat.

6,7-Dihydroxy-2-dimethylaminotetralin (TL-99), the 5,6-dihydroxy isomer (M-7) and dopamine were studied for cardiovascular activity in the cat and dog. TL-99 was found to be the most active of these compounds. Some of the more striking actions of TL-99 and M-7 were bradycardia, hypotension and complete blockade of norepinephrine-induced reflex activation. A detailed study of these compounds showed that they were most likely exerting their effects by inhibiting sympathetic nervous system activity. Whether these compounds were activating dopamine receptors or alpha adrenergic receptors is not entirely clear from this study.

Adrenergic beta-Antagonists↗
PubMed1977

Aminotetralins as selective beta-adrenergic agonists.

Aminotetralin derivatives M-8 and JOD-176, were studied in relation to isoproterenol for beta-adrenergic activity. M-8 and JOD-176 were found to be very weak in activating cardiac beta-receptors. These compounds were also found to be considerably more active in uterine and bronchial smooth muscle. Because these compounds were also shown to be very inactive in vascular smooth muscle, the possibility that beta-receptors in different smooth muscle types may also differ was suggested.

1-Naphthylamine↗
PubMed1976

Alpha-adrenergic activity of N,N-dimethyldopamine (DMDA).

The autonomic and cardiovascular activity of N,N-dimethyldopamine (DMDA) was studied in the dog and rabbit. DMDA appears to be a postganglionic sympathetic alpha-adrenoceptor agonist since it consistently caused vasconstriction in several isolated vascular beds, even in the presence of ganglionic blockade. The pressor activity of DMDA was attenuated by the alpha-adrenergic antagonist phentolamine. Calculated pA2 values for phentolamine against both DMDA and norepinephrine in isolated rabbit arteries were in close agreement. DMDA inhibits cardioaccelerator nerve stimulation induced chronotropic responses by a mechanism which appears to be alpha-adrenergic in the dog.

Adrenergic alpha-Agonists↗