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Species differences in the in vitro metabolic reduction of the amphetamine metabolite, 1-phenyl-2-propanone.

Marked differences were observed, in the ability of fortified 9000 g liver homogenate supernatants from three species to reduce 1-phenyl-2-propanone to the corresponding alcohol. This metabolic keto-reduction was negligible in homogenates from the rat and extensive in the rabbit; guinea-pig liver homogenates had intermediate ability. Metabolic oxidation of 1-phenyl-2-propanol was negligible in all three species. The amount of deamination of amphetamine and of N-n-propylamphetamine was approximately equal, in vitro, in rats and guinea-pigs but two to three times greater in liver homogenates from rabbits. Approximately three times more deaminated products were formed from the in vitro metabolism of N-n-propylamphetamine than from amphetamine metabolism by all three species.

Acetone↗

Effect of bupropion on dopamine and 5-hydroxytryptamine-mediated behaviour in mice.

When bupropion (12.5-50 mg kg-1) was administered 30 min before methamphetamine it significantly antagonized methamphetamine-induced stereotyped behaviour in mice, but when given 5 min after methamphetamine it significantly potentiated the behaviour. When it was administered to mice pretreated with 100 mg kg-1 pargyline, intense locomotor stimulation and stereotyped behaviour was observed whereas when clomipramine was administered similarly the animals showed locomotor stimulation, head twitches and abduction and extension of hind limbs. Unlike clomipramine, bupropion failed to potentiate the 5-hydroxytryptamine-mediated behaviour seen after 5-hydroxytryptophan, 100 mg kg-1, i.v. These observations are in agreement with reports that bupropion is more potent as an inhibitor of dopamine uptake than as an inhibitor of 5-hydroxytryptamine uptake in-vitro.

5-Hydroxytryptophan↗

Pharmacological characterization of postsynaptic alpha-adrenoceptor subtypes in five different dog arteries in-vitro.

The responses of helically cut strips of arteries isolated from five different sites in the body of dogs to relatively selective alpha 1- and alpha 2-adrenoceptor agonists and the antagonism exerted on these responses by relatively selective alpha 1- and alpha 2-adrenoceptor blockers have been studied. On all arteries (renal, splenic, cranial mesenteric, jejunal and femoral) phenylephrine was a full agonist whereas UK-14,304 was a partial agonist causing maximal contractions of 49, 30, 27, 27 and 10% of the maximum, respectively. Phenylephrine was more potent than UK-14,304, being 9 times more potent in the renal artery and up to 42 times more potent in the cranial mesenteric artery. In the dog saphenous vein, where there are both alpha 1- and alpha 2-adrenoceptors, it has been previously shown that UK-14,304 is 530 times more potent than phenylephrine. Prazosin in low concentrations displaced concentration-response curves for both phenylephrine and UK-14,304 (pA2 values of 8.16-8.43 and 8.13-8.79, respectively) whereas yohimbine was much less potent (pA2 values of 6.53-6.88 and 6.50-7.20, respectively). The results suggest that the alpha-adrenoceptors of all arteries studied are predominantly, if not exclusively, of the alpha 1-subtype.

Animals↗