Clyde M. Williams

Activities of octopamine and synephrine stereoisomers on α‐adrenoceptors

1 The activities of the (‐)‐ and (+)‐forms of m‐ and p‐octopamine and m‐ and p‐synephrine on α1‐adrenoceptors from rat aorta and anococcygeus and α2‐adrenoceptors from rabbit saphenous vein were compared with those of noradrenaline (NA). 2 The rank order of potency of the (‐)‐ forms on α1‐adrenoceptors from rat aorta and α2‐adrenoceptors was NA > m‐octopamine = m‐synephrine > p‐octopamine = p‐synephrine. The two m‐compounds were 6 fold less active than NA on α1‐adrenoceptors from rat aorta and 150 fold less active on α2‐adrenoceptors. The two p‐compounds were 1,000 fold less active than NA on both α1‐adrenoceptors from rat aorta and α2‐adrenoceptors. The rank order of potency of the (‐)‐ forms on α1‐adrenoceptors from rat anococcygeus was NA = m‐synephrine > m‐octopamine > p‐octopamine = p‐synephrine. m‐Octopamine was 4 fold less active than NA and (‐)‐m‐synephrine. The two p‐compounds were 30 fold less active than NA. 3 The rank order of potency of the (+)‐ forms was NA > m‐octopamine > m‐synephrine > p‐octopamine > p‐synephrine on both α1‐ and α2‐adrenoceptors. The potency of each (+)‐ form was 1–2 orders of magnitude less than that of the (‐) counterpart, the differences being greater for the stereoisomers of synephrine than for those of octopamine on both α1‐ and α2‐adrenoceptors. 4 The yohimbine diastereoisomer antagonists, rauwolscine and corynanthine, were tested against (‐)‐NA and (‐)‐m‐octopamine‐induced contractions in both preparations. Based upon the known selectivities of these isomers for α‐adrenoceptor subtypes, it is concluded that the rat aorta contains only α1‐adrenoceptors while the rabbit saphenous vein possesses predominantly α2‐adrenoceptors. 5 Ligand binding data for the octopamine and synephrine stereoisomers at α1‐ and α2‐binding sites from rat cerebral cortex was also obtained. (‐)‐Forms were more active than (+)‐forms. The rank order of affinity of the (‐)‐forms for both α1‐ and α2‐binding sites was NA > m‐octopamine = m‐synephrine > p‐synephrine > p‐octopamine. The relative affinities of the members of the series against α1‐binding sites were very similar to their relative functional activities on rat aorta. However, the affinities of both m‐ and p‐compounds relative to that of (‐)‐NA were much greater at the α2‐binding sites than were the relative activities in rabbit saphenous vein, possibly suggesting low intrinsic efficacy. Functional antagonist responses to NA by the (‐)‐octopamine and synephrines could not, however, be demonstrated on rat aorta or rabbit saphenous vein. 6 The activities of m‐octopamine and m‐synephrine were not significantly different from each other on either α1‐adrenoceptors from rat aorta or α2‐adrenoceptors; however, m‐synephrine is more active than m‐octopamine on α1‐adrenoceptors from rat anococcygeus. Both m‐octopamine and m‐synephrine can be considered to be naturally occurring α1‐selective amines. However, if m‐ and p‐octopamine are co‐released with NA in amounts proportional to their concentration, it is concluded that their activities on α1‐ and α2‐adrenoceptors are too low to be physiologically significant.

β-Adrenergic activities of octopamine and synephrine stereoisomers on guinea-pig atria and trachea

The activities of the (‐)‐ and (+)‐forms of m‐ and p‐octopamine and m‐ and p‐synephrine on β1‐ and β2‐ adrenoceptors in guinea‐pig atria and trachea have been compared with that of noradrenaline. The rank order of potency of the (‐)‐forms on β1‐adrenoceptors was noradrenaline > m‐synephrine. m‐octopamine = p‐octopamine > p‐synephrine. m‐Synephrine was 100‐fold, m‐and p‐octopamine about 6000‐fold, and p‐synephrine about 40 000‐fold less active than noradrenaline. The (+)‐forms were 1‐2 orders of magnitude less active than their (‐)‐counterparts. The four (‐)‐compounds were more than four orders of magnitude less active than noradrenaline on β2,‐adrenoceptors, and the (+)‐forms had no detectable activity in concentrations as high as 10−4 M. If m‐and p‐octopamine are co‐released with noradrenaline in amounts proportional to their concentration, their activities at these structures are too low to be physiologically significant.

Gas chromatography of urinary aromatic acids

Abstract A method is described for the separation and identification of 29 aromatic acids by gas chromatography. Aromatic acids without phenolic groups are converted to their methyl esters by reaction with ethereal diazomethane and chromatographed on an 8% ethylene glycol adipate column at 170°C. Phenolic acids are converted to their methyl ester derivatives by ethereal diazomethane and chromatographed on a 3% neopentyl glycol adipate column at 187°C. When other compounds in the urinary extracts overlap with these peaks, a second derivative, the methyl esterified O -methyl ether is prepared by reaction with diazomethane and methanol overnight, and chromatographed on the same column. Indolic acids are converted to their methyl esters with diazomethane and chromatographed on a 2% silicone (SE-30) column at 180°C. When the indolic hydroxyl groups are present, as in 5-hydroxyindoleacetic acid, the methyl esterified O -methyl ether derivative may be prepared if necessary and chromatographed at the same temperature. In certain cases such as vanilmandelic acid, the preferred derivative has an inconveniently long retention time at 187°C on the polar column and an inconveniently short retention time at 180°C on the nonpolar column. This derivative may best be determined at a higher temperature (210–225°) on the polar column.

Cadmium Telluride Gamma Camera

A small 4 cm X 4 cm prototype CdTe gamma camera has been constructed which demonstrates sensitivity and spacial resolution superior to the standard Anger camera. The camera is based on an array of linear solid state detectors contained within a laminar collimator which confines the field of view to one dimension. The array is rotated stepwise through 180° and data from each position recorded and computer processed. This technique leads to a major enhancement in sensitivity relative to the multihole collimator. Clinical images have been obtained and a larger CdTe camera is planned.

Isomeric octopamines: their occurrence and functions

p-Octopamine is a widely distributed invertebrate neurotransmitter (Evans 1978). It also occurs in the mammalian sympathetic nervous system, where its function is unknown (Axelrod & Saavedra 1977). Recent advances (Ibrahim et al 1984, 1985) in mass spectrometric analytical techniques have disclosed that, in addition to p-octopamine, 0and m-octopamine and the N-methyloctopamines (mand p-synephrine) also occur naturally in mammals. Evidence indicates that mand p-octopamine are located in sympathetic nerves with noradrenaline whereas mand p-synephrine are found only in adrenal gland (Ibrahim et al 1985). The location of o-octopamine is unknown but it is probably not in the same anatomical structure as mand p-octopamine and noradrenaline (Ibrahim & Williams 1985). This review summarizes the present knowledge concerning the distribution and possible functions of the three positionally isomeric octopamines.

The mammalian metabolism of R-(-)-m-synephrine

The metabolism of R‐(‐)‐m‐synephrine (administered orally and by inhalation in man and intraperitoneally in rats) was studied quantitatively by a gas chromatography‐mass spectrometry‐selected ion monitoring (g.c.–m.s.–s.i.m.) method using deuterated internal standards. When m‐synephrine hydrochloride was administered orally to humans in normal dosage regimens four main metabolites were excreted in urine: (i) unconjugated m‐hydroxymandelic acid (MHMA, 30%), (ii) m‐hydroxyphenylglycol (MHPG) sulphate (6%), (iii) m‐synephrine sulphate (47%) and (iv) m‐synephrine glucuronide (12%). The comparable figures after inhalation of the drug were 24, 6, 56 and 5%. Intraperitoneal injection of m‐synephrine into rats gave: unconjugated MHMA (5%), MHPG sulphate (35%), unconjugated m‐synephrine (7%) and conjugates of m‐synephrine (9%:4% as the glucuronide and 5% as the sulphate).

Determination of urinary 3-methoxytyramine, normetanephrine and metanephrine in pheochromocytoma and neuroblastoma by gas chromatography☆

Abstract A gas chromatographic method for the determination of 3-methoxytyramine, metanephrine and normetanephrine has been developed and applied to their determination in the urine of patients with neuroblastoma and pheochromocytoma.

Unrecognized left ventricular dysfunction in an apparently healthy alcohol abuse population

To examine effects of chronic alcohol abuse on left ventricular function, 162 otherwise relatively healthy alcohol abusers, having been admitted to a rehabilitation program, underwent cardiac evaluation including chest X-ray, electrocardiogram, and radionuclide angiography after 2 weeks abstinence. Twenty-nine of the 162 alcoholic subjects (18%) with left ventricular dysfunction were identified. Twenty-two had regional wall motion abnormalities, suggesting a localized process, of whom 12 also had depressed ejection fractions. Seven others had a depressed ejection fraction alone with a more global myopathic process. Only 4 of these 29 patients had any history suggesting prior heart disease. Two of the 29 had Q-waves greater than or equal to 0.4 s and 8 had an abnormal cardiothoracic ratio on chest X-ray. Chronic alcohol abusers appear to be at relatively high risk for left ventricular dysfunction; most of which is unrecognized. Routine screening methods failed to identify 85% of our subjects who later were recognized by radionuclide angiography. Since historical and electrocardiographic abnormalities are often absent in this population, detection of left ventricular dysfunction by other methods such as radionuclide angiography must be used.

Identification of ortho-octapamine and meta-octopamine in mammalian adrenal and salivary gland

Abstract Ortho - and meta - octopamine have been identified in beef and rat adrenal gland and in rat salivary gland by means of gas chromatography-mass spectrometry. The tritrifluoroacetyl derivatives of ortho -, meta - and para - octopamine were resolved by gas chromatography and shown to produce two characteristic ions at m/e 315 and m/e 328. The di-O-trimethylsilyl-N-trifluoroacetyl derivatives of these three isomers were also resolved by gas chromatography and shown to produce a characteristic ion at m/e 267. Biological samples were homogenized in formic acid:acetone, subjected to ion-exchange chromatography and then derivatized. When the derivatized biological extracts were examined for each characteristic ion, peaks were observed at the exact retention times of the standards. The three isomers are present in adrenal gland in concentrations of ∼1 μg g−1 and in rat salivary gland in concentrations of ∼0.1 μg g−1. This evidence confirms a previous report of the presence of m -octopamine in rat salivary gland measured by a radiochemical enzyme assay and is the first report of the presence of o -octopamine in biological tissue.

Mass spectrometry of tryptamines and acetylated tryptamine derivatives.

Abstract Eleven mass spectra of biologically important tryptamines and their acetylated derivatives are recorded in this paper. For diagnostic purposes, the N -acetyltryptamines are preferred over other derivatives because they undergo the fewest significant rearrangements upon electron impact. Two prominent modes of decomposition are noted for the tryptamines: (1) loss of CHNR 2 and H or CH 2 NR 2 by the molecular ion to give the [MCH 2 NR 2 ] ion which further fragments as a quinolinium ion and (2) formation of the CH 2 NR 2 ion. The N -acetyltryptamines are characterized by intense [MC 3 H 6 NO] ions, arising via a variety of different pathways. These ions correspond to the [MCH 2 NR 2 ] ions of the parent compounds and fragment similarly. 1-Acetyl- N,N -dimethyltryptamines give intense [CH 2 NR 2 , RCH 3 ] ions and weak m e 43 (COCH 3 ) ions. All other ions have less than 5% relative intensity.