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T R LaHann

Publications and source records attributed to T R LaHann.

10 recordsLinked to original sources
PubMed1993

Vanilloids. 1. Analogs of capsaicin with antinociceptive and antiinflammatory activity.

As part of a program to establish structure-activity relationships for vanilloids, analogs of the pungent principle capsaicin, the alkyl chain portion of the parent structure (and related compounds derived from homovanillic acid) was varied. In antinociceptive and antiinflammatory assays (rat and mouse hot plate and croton oil-inflamed mouse ear), compounds with widely varying alkyl chain structures were active. Short-chain compounds were active by systemic administration in the assays mentioned above but they retained the high pungency and acute toxicity characteristic of capsaicin. In contrast, the long chain cis-unsaturates, NE-19550 (vanillyloleamide) and NE-28345 (oleylhomovanillamide), were orally active, less pungent, and less acutely toxic than capsaicin. The potential of these compounds as antiinflammatory/analgesic agents is discussed in light of recent data on the mechanism of action of vanilloids on sensory nerve fibers.

Analgesics↗
PubMed1989

Topographic probes of angiotensin and receptor: potent angiotensin II agonist containing diphenylalanine and long-acting antagonists containing biphenylalanine and 2-indan amino acid in position 8.

A series of phenylalanine-mimicking amino acids with increasing conformational restraint were prepared and incorporated into angiotensin II, in order to develop topographic probes of angiotensin useful for probing receptor boundaries by molecular graphics analysis and for conformational analysis of the ligand by NMR. In binding studies, all analogues displayed high affinity for rat uterus (Ki of 0.74-6.08 nM) and brain (0.46-1.82 nM) receptors. In smooth muscle (rat uterus) contraction assay, the diphenylalanine-containing [Sar1,Dip8]AII and [Sar1,D-Dip8]AII were potent agonists with respectively 284% and 48% activity of [Asn1]AII. In contrast, the biphenylalanine-containing [Sar1,Bip8]AII, [Sar1,D-Bip8]AII, and the 2-indan amino acid containing [Sar1,2-Ind8]AII were potent inhibitors, approximately 9, 2, and 1.4 times more effective than a standard antagonist, [Sar1,Leu8]AII. Their respective pA10 values in rat uterus assay were 8.87, 8.70, and 8.82. By comparison, the pA10 value for [Sar1,Leu8]AII was 8.35. In rats, a single dose of 10 micrograms of [Sar1,2-Ind8]AII or [Sar1,Bip8]AII produced prolonged blockade of the pressor response toward angiotensin II for over 90 min. The very different pharmacological profiles of these rigid aromatic analogues suggest that the angiotensin receptor activation site consists of a relatively wide and elongated pocket with a narrow opening.

Affinity Labels↗
PubMed1982

Thyrotropin releasing hormone: centrally mediated effects on gastrointestinal motor activity.

The central, but not the peripheral, administration of thyrotropin releasing hormone (TRH) elicited an increase in the gastrointestinal (GI) motor activity in anesthetized rabbits. This effect did not appear to be mediated via the pituitary-thyroid axis and it was relatively independent of the degree of basal motor activity in the Gl tract. Intravenous administration of either atropine or ganglionic blocking agents antagonized this phenomenon. Bilateral vagal transection prevented the TRH-induced stimulation of Gl motor activity, but neither spinal transection nor i.v. guanethidine had any effect. When injected into the lateral ventricles, 3rd ventricle of cisterna magna, TRH always elicited its Gl effects. Central cholinergic mechanisms appear to be involved because both atropine methyl bromide and atropine sulfate given i.c.v. antagonized the Gl effects. Intravenous injection of phenoxybenzamine also inhibited the TRH effect. TRH stimulates neural pathways within the central nervous system to activate efferent vagal fibers leading to a generalized increase in the motor activity of the Gl tract.

Animals↗