Biomedical subjects

J Zongrone

Publications and source records attributed to J Zongrone.

4 recordsLinked to original sources

PubMed2000

(-)-Spiro[1-azabicyclo[2.2.2]octane-3,5'-oxazolidin-2'-one], a conformationally restricted analogue of acetylcholine, is a highly selective full agonist at the alpha 7 nicotinic acetylcholine receptor.

Neuronal nicotinic acetylcholine receptors are members of the ligand-gated ion channel receptor superfamily and may play important roles in modulating neurotransmission, cognition, sensory gating, and anxiety. Because of its distribution and abundance in the CNS, the alpha 7 nicotinic receptor is a strong candidate to be involved in some of these functions. In this paper we describe the synthesis and in vitro profile of AR-R17779, (-)-spiro[1-azabicyclo[2.2. 2]octane-3,5'-oxazolidin-2'-one] (4a), a potent full agonist at the rat alpha 7 nicotinic receptor, which is highly selective for the rat alpha 7 nicotinic receptor over the alpha 4 beta 2 subtype. Preliminary SAR of AR-R17779 presented here indicate that there is little scope for modification of this rigid molecule as even minor changes result in significant loss of the alpha 7 nicotinic receptor affinity.

Acetylcholine↗

PubMed1997

Synthesis and biological evaluation of potent, selective, hexapeptide CCK-A agonist anorectic agents.

Cholecystokinin (CCK) is a 33-amino acid peptide with multiple functions in both the central nervous system (via CCK-B receptors) and the periphery (via CCK-A receptors). CCK mediation of satiety via the A-receptor subtype suggest a role for CCK in the management of obesity. The carboxy terminal octapeptide (CCK-8) is fully active in this regard, but is lacking in receptor selectivity, metabolic stability, and oral bioavailability. Inversion of the chirality of Asp7 in conjunction with N-methylation of Phe8 produces compound 5 which exhibits high affinity and 2100-fold selectivity for CCK-A receptors. Compound 6 (Hpa(SO3H)-Nle-Gly-Trp-Nle-MeAsp-Phe-NH2), derived from moving the N-methyl group from Phe to Asp, decreased CCK-B affinity substantially without affecting CCK-A affinity, giving a compound with 6600-fold selectivity for CCK-A receptors. These compounds inhibit food intake with nanomolar potency following intraperitoneal administration in fasted rats. In addition to greater potency, compound 6 produces weight loss in rats when administered over nine consecutive days. Intranasal administration of 6 potently inhibits feeding in beagle dogs. Compound 6 produces potent anorectic activity via the CCK-A receptor system.

Administration, Intranasal↗

PubMed1987

Human chorionic gonadotropin, estriol, and testosterone changes in two pregnancies with hyperreactio luteinalis.

A case of hyperreactio luteinalis is presented with measurements of human chorionic gonadotropin, total and free testosterone, and estriol throughout two term pregnancies. Ovulation induction with menotropins resulted in one spontaneous first-trimester abortion, one singleton term pregnancy, and 1 triplet pregnancy that converted to a singleton term pregnancy after spontaneous degeneration of two fetuses in the first trimester. During the first term pregnancy, levels of human chorionic gonadotropin peaked at 34 weeks of gestation (169,000 mIU/ml) and levels of total testosterone peaked at the same time (1777 ng/dl). Free testosterone (16.6 ng/dl) and estriol (10.8 ng/ml) reached their peak at 36 weeks of gestation. During the second term pregnancy, peak values of human chorionic gonadotropin (150,900 mIU/ml) and total testosterone (870 ng/dl) occurred at 10 and 5 weeks of gestation, respectively, before two fetuses of a triplet pregnancy degenerated.

Adult↗

PubMedDate not supplied

Superovulation of habitual aborters with subtle luteal phase deficiency.

Five habitual aborters without a known organic cause of their pregnancy losses were studied in detail by serial blood sampling for immunoreactive estrogen, progesterone, follicle-stimulating hormone, luteinizing hormone, and the ratio of the two. All patients had premenstrual spotting regularly. Luteal phase progesterone levels on the 6th postovulatory day were significantly lower (11.8 +/- 1.2 ng/mL, mean +/- SEM) than in control patients (20.8 +/- 3.5 ng/mL, mean +/- SEM). Results of immunoreactive estrogen, FSH, and LH assays and the FSH/LH ratio did not reveal a discernible pattern of deviation from normal. Indirect immunofluorescence of blood samples from all habitual aborters showed evidence of autoimmunity in three of five patients without clinical symptoms of autoimmune disease. Treatment by superovulation produced at least one living child in each couple. The balance of pregnancy outcome changed from 100% abortion (N = 31) before treatment to 31% (N = 13) after treatment. These results suggest that treatment with superovulation may be the treatment of choice for habitual aborters with a subtle luteal phase deficiency.

Abortion, Habitual↗