Influence of saponins and tannins on intake and nutrient digestion of alkaloid-containing foods.

BACKGROUND: We hypothesized that eating a food containing saponins (SAP), or tannins (TAN) prior to foods containing the alkaloids gramine (GRA) or 5-methoxy-N,N-dimethyltryptamine (TRP) would provide benefits not possible when the alkaloid-containing foods were eaten alone. METHODS: In Trial 1, four groups of five lambs were first offered food with SAP for 30 min followed by food with either GRA or TRP for 3.5 h in a 2 × 2 factorial arrangement of a completely randomized design that included alkaloid (GRA or TRP) with or without SAP. In Trial 2 TAN replaced SAP. All foods were isocaloric (3.3 Mcal kg⁻¹) and isonitrogenous (14% crude protein). Foods, fecal and urine samples were collected and analyzed for dry matter intake and apparent digestibility of dry matter, energy (in megajoules, MJ), nitrogen (N), and neutral detergent fiber. RESULTS: Supplemental SAP did not affect digestibility of the parameters tested (P > 0.10). Supplemental TAN increased digestibility of N (g kg⁻¹, P = 0.04), N retained (g day⁻¹, P = 0.07), N digested (g day⁻¹, P = 0.06), and N retained/N consumed (g kg⁻¹, P = 0.07). However, digestibilities of dry matter (g kg⁻¹, P = 0.0026), energy (MJ 1000 MJ⁻¹, P = 0.003), neutral detergent fiber (g kg⁻¹, P = 0.008), and digested N retained (g kg⁻¹, P = 0.07) were lower for lambs fed TAN than for unsupplemented animals. CONCLUSIONS: Tannin supplementation can improve retention of nitrogen in animals fed alkaloid-containing grasses such as reed canarygrass and tall fescue. Combinations of forages with complementary primary and secondary compounds enable animals to maintain intake and improve nutrient utilization.

Mechanism of action of aripiprazole predicts clinical efficacy and a favourable side-effect profile.

The antipsychotic efficacy of aripiprazole is not generally associated with extrapyramidal symptoms, cardiovascular effects, sedation or elevations in serum prolactin that characterize typical or atypical antipsychotics. The aim of this study was to clarify the mechanism of action of aripiprazole that underlies its favourable clinical profiles. The preclinical efficacy and side-effect profiles of aripiprazole were evaluated using several pharmaco-behavioural test systems in mice and rats, both in vivo and ex vivo, and compared with those of other conventional and atypical antipsychotics. Each of the antipsychotics induced catalepsy and inhibited apomorphine-induced stereotypy. The catalepsy liability ratios for these drugs were 6.5 for aripiprazole, 4.7 for both olanzapine and risperidone. The ptosis liability ratios for aripiprazole, olanzapine and risperidone were 14, 7.2 and 3.3, respectively. Aripiprazole slightly increased DOPA accumulation in the forebrain of reserpinised mice, reduced 5-HTP accumulation at the highest dose and exhibited a weaker inhibition of 5-methoxy-N,N-dimethyl-tryptamine-induced head twitches. Aripiprazole did not inhibit physostigmine- or norepinephrine-induced lethality in rats. In conclusion, aripiprazole shows a favourable preclinical efficacy and side-effect profile compared to a typical antipsychotics. This profile may result from its high affinity partial agonist activity at D2 and 5-HT1A receptors and its antagonism of 5-HT2A receptors.