A. M. Duffield

Identification of some human urinary metabolites of the intoxicating beverage kava

Methane chemical ionization (CI) gas chromatography-mass spectrometry (GC-MS) has been used to identify some of the human urinary metabolites of the kava lactones following ingestion of kava prepared by the traditional method of aqueous extraction of Piper methysticum. All seven major, and several minor, kava lactones were identified in human urine. Observed metabolic transformations include the reduction of the 3,4-double bond and/or demethylation of the 4-methoxyl group of the alpha-pyrone ring system. Demethylation of the 12-methoxy substituent in yangonin (or alternatively hydroxylation at C-12 of desmethoxyyangonin) was also recognised. This product was isolated by high-performance liquid chromatographic analysis of crude urine extracts and characterised by methane CI GC-MS. In contrast to the situation prevailing in the rat no dihydroxylated metabolites of the kava lactones, or products from ring opening of the 2-pyrone ring system, were identified in human urine. GC-MS analysis of urine can be readily utilised to determine whether donors have recently consumed kava.

Distribution and chemical composition of the toxic skin secretions from trunkfish (family Ostraciidae)

The components of the mucus skin secretions from eight species of trunkfish found in the coastal waters of Australia were analyzed by combined chemical ionization-gas chromatography mass spectrometry. The species investigated were Anoplacapros lenticularis, Aracana aurita, Aracana ornata, Lactoria fornasini, Ostracion cubicus, Rhinesomas reipublicae, Strophiurichthys inermis and Strophiurichthys robustus. The beta-substituted choline chloride esters (mainly acetoxy, but with some species having butyryloxy, valeryloxy and one species with caproyloxy) of palmitic acid were the predominant components in almost all cases. High concentrations of monounsaturated palmitic acid were present in S. inermis and S. robustus. Trace quantities of C14, C17 and C18 choline chloride esters were also detected as were compounds where the choline moiety was modified by addition of one extra carbon.

Stereoselective accumulation of hydroxylated metabolites of amphetamine in rat striatum and hypothalamus

1 The stereoselective accumulation of α‐methyl‐p‐tyramine (AMPT) and α‐methyl‐p‐octopamine (AMPO) in rat striatum and hypothalamus after acute and chronic administration of the (+)‐and (−)‐isomers of amphetamine (Amphet) and the acute administration of (+)‐ and (−)‐AMPT has been investigated by chemical ionization gas chromatography mass spectrometry (c.i.g.c.m.s.). 2 Two h after the administration of (+)‐ or (−)‐AMPT (5 mg kg−1 i.p.), the concentrations of the isomers in striatal tissue were approximately equal; 18 h later, the concentration of the (+)‐isomer was 10 times that of the (−)‐isomer. 3 The concentrations of AMPO in the striatum and hypothalamus 20 h after administration of (+)‐AMPT were 68 ng g−1 and 484 ng g−1 respectively. After the administration of the (−)‐isomer of AMPT, small quantities of AMPO were detected in both brain areas. 4 Twenty h after the last of 7 daily injections of (+)‐Amphet (5 mg kg−1, i.p.), the concentration of AMPO in the hypothalamus was 5.4 times the concentration at 20 h after one injection. In the striatum, the corresponding ratio for AMPO was 3.5 and for AMPT was 2.5. 5 These data indicate that, although both isomers of AMPT formed from Amphet administered systemically, cross the blood brain barrier, the (+)‐isomers AMPT and AMPO are preferentially stored in striatal and hypothalamic aminergic nerve terminals. 6 The accumulations of AMPT and AMPO in rat striatum and hypothalamus after chronic administration of Amphet demonstrates that these metabolites persist in neuronal storage in these brain areas for days after administration. The half‐lives of (+)‐AMPT and (+)‐AMPO in striatal neuronal storage, calculated from this data, were 1.5 days and 2.5 days, respectively. The corresponding half‐life for hypothalamic (+)‐AMPO was 7 days. 7 These findings suggest the involvement of accumulated AMPT and AMPO in the development of behavioural augmentation to repeated injections of Amphet (Randrup & Munkvad, 1970).

The effects of (+)-amphetamine, alpha-methyltyrosine, and alpha-methylphenylalanine on the concentrations of m-tyramine and alpha-methyl-m-tyramine in rat striatum.

1 The concentration in rat striatum of the meta and para isomers of tyramine and α‐methyltyramine, after the administration of (+)‐amphetamine, α‐methyl‐p‐tyrosine (AMPT) and α‐methylphenylalanine (AMPA) has been determined using chemical ionization gas chromatography mass spectrometry (c.i.g.c.m.s.). 2 Twenty hours after the last of 7 daily injections of (+)‐amphetamine (5 mg kg−1 i.p.) the concentration of α‐methyl‐p‐tyramine in striatal tissue increased twofold compared to the concentration 20 h after a single injection. In contrast the concentration of α‐methyl‐m‐tyramine did not change. 3 α‐Methyl‐m‐tyramine and α‐methyldopamine were found in the striatum at concentrations of 42 ng g−1 and 13.5 ng g−1 respectively after treatment of rats 20 h before with AMPA (100 mg kg−1 i.p.). After treatment with AMPT (100 mg kg−1, 20 h before decapitation) only the para isomer of α‐methyltyramine could be detected (13.7 ng g−1) although the striatal concentration of α‐methyldopamine was 274 ng g−1, a level 20 times greater than that observed after AMPA treatment. The combined administration of both AMPT and AMPA (100 mg kg−1 each, 20 h) resulted in a reduction of the striatal concentration of α‐methyl‐m‐tyramine but not α‐methyl‐p‐tyramine. 4 These data suggest that α‐methyl‐m‐tyramine in rat striatum is formed by the enzyme tyrosine hydroxylase on substrate AMPA, rather than by ring dehydroxylation of α‐methyldopa and ***α‐methyldopamine. Significant reductions in the striatal concentrations of m‐tyramine 2 h after the administration of AMPT, suggest that tyrosine hydroxylase is involved similarly in the production of m‐tyramine.

The concentration in brain of octopamine and tyramine after portal-systemic bypass in rats: Neuroamine concentrations determined simultaneously by methane chemical ionization gas chromatography mass spectrometry

The concentration in brain of both octopamine (OCT) and tyramine (TYR) was significantly increased in rats 8 weeks after portal-systemic bypass. This suggests that the increase in OCT is secondary to increased decarboxylation of tyrosine to TYR. However, the role these neuroamines, particularly OCT, play in the development of hepatic encephalopathy remains controversial.

Effect of chlordimeform and clonidine on the turnover of P-octopamine in rat hypothalamus and striatum.

The effect of the invertebrate octopamine agonists chlordimeform and clonidine on the concentration and turnover of p-octopamine and m- and p-tyramine was determined in rat hypothalamus and striatum. Clonidine (0.25 mg/Kg, s.c.) did not alter the concentration of p-octopamine in the hypothalamus or p-tyramine in the striatum. Administration of chlordimeform (50 mg/Kg, i.p.) resulted in an increase in p- and m-tyramine concentrations in the striatum but not that of p-octopamine in the hypothalamus. This increase in the tyramine isomers is consistent with the ability of chlordimeform and its metabolite, demethylchlordimeform, to inhibit monoamine oxidase (MAO). The concurrent administration of chlordimeform (50 mg/Kg, i.p.) and pargyline (75 mg/Kg, i.p.) produced a significant decrease in the accumulation of octopamine in the hypothalamus but not in the striatum. In contrast, the concurrent administration of clonidine (0.25 mg/Kg, s.c.) and pargyline (75 mg/Kg, i.p.) caused a significant decrease in the accumulation of octopamine in the striatum but not hypothalamus. These results show that the turnover of octopamine in the hypothalamus and striatum is decreased by chlordimeform and clonidine, respectively. Further, clonidine is known to modulate the turnover of amines in mammalian noradrenergic nerve terminals by an action at presynaptic adrenergic receptors. These data suggest that two mechanisms, one involving presynaptic adrenergic receptors in the striatum, and the other involving as yet unidentified receptors in the hypothalamus, modulate the turnover of octopamine in the mammalian brain.

Occurrence and synthesis of octopamine in the heart and ganglia of the mollusc Tapes watlingi

Abstract 1. 1. Gas chromatography chemical ionization mass spectrometry was used to measure the octopamine, tyramine, β-hydroxyphenethylamine and dopamine content of nervous, cardiovascular and gastrointestinal tissues in the clam Tapes watlingi . 2. 2. The nervous tissues contained higher concentrations of octopamine than either cardiovascular or gastrointestinal tissue. 3. 3. Nervous and ventricular tissue synthesized deuterated octopamine, from exogenous deuterated tyramine. These data support the suggestion that octopaminergic nerves may be present in the molluscan heart.

Absence of α-methyldopamine in rat striatum after chronic administration of d-amphetamine

Direct measurement by gas chromatography methane chemical ionization mass spectrometry of alpha-methyldopamine and alpha-methylnorepinephrine in rat striatum has shown the failure of these compounds to be accumulated in vivo after chronic administration of d-amphetamine despite the accumulation of alpha-methyltyramine, an immediate in vitro precursor. Further, both alpha-methyldopamine and alpha-methyltyramine accumulate in rat striatum after administration of alpha-methyltyrosine. These data suggest that, after administration of alpha-methyltyrosine, alpha-methyldopamine is formed via decarboxylation of alpha-methyldopa and not from hydroxylation of alpha-methyltyramine. Finally, our results indicate that alpha-methyldopamine does not play a role in the development of tolerance to d-amphetamine.

SULFENAMIDES AND SULFINAMIDES IV. HOMOLYSIS OF SULFENAMIDES IN CYCLOHEXENE

Abstract The photocatalysed decomposition of aromatic sulfenamides in cyclohexene is a rapid reaction at ambient temperature. Products fall into two main groups resulting from recombination of initially formed radicals and from intervention of solvent acting as a radical trap.