I The activity of bromocriptine has been investigated in tests for the stimulation of central dopaminergic mechanisms. The results obtained have been compared with those of apomorphine, (+)-amphetamine and L-DOPA. 2 Bromocriptine (2.5 to 10 mg/kg) induced stereotyped sniffing and licking in rats. The stereotypy was more intense than that induced by L-DOPA and less intense than that of apomorphine and (+)-amphetamine over the dose ranges studied. 3 In rats lesioned unilaterally in the substantia nigra by local injection of 6-hydroxydopamine, bromocriptine, like apomorphine and L-DOPA, induced turning contralateral to the side of the lesion. The smallest dose of bromocriptine to induce turning was 0.5 mg/kg. 4 Reserpine-induced catalepsy in mice was antagonized by bromocriptine, with an ED50 of 1.8 mg/kg. It was intermediate in potency to apomorphine and L-DOPA.
5Spontaneous locomotor activity in mice was stimulated by bromocriptine in a dose-dependent manner from 2.5 to 10 mg/kg after an initial suppression of activity. 6 In all experiments, bromocriptine was characterized by a prolonged duration of activity after a delay in the onset of effect. 7 The stereotyped behaviour induced by bromocriptine was inhibited by prior administration of pimozide, reserpine or a-methyl-p-tyrosine. 8 Bromocriptine-induced turning behaviour was abolished by pretreatment with pimozide, and reduced after a-methyl-p-tyrosine pretreatment. 9 The results obtained support the conclusion that bromocriptine acts by stimulating dopamine receptors in the central nervous system and that intact catecholamine synthesis and granular amine storage mechanisms are necessary for it to bring about its effects.
Herbal medicinal products (HMP) contain exclusively herbal drugs or herbal drug preparations (HDP) and are a complex mixture of different compounds, which may act in an agonistic, synergistic, complementary, antagonistic or toxic way. A specific scientific challenge is for methods to prone the bioequivalence of herbal drug preparations (HDP). Depending on the type of herbal drug preparations, different approaches are possible. If the constituents responsible for therapeutic activity are known, the concept of essential similarity used with chemically defined substances can be fully applied. For extracts with unknown active markers, data on defined chemical constituents are useful for control purposes (charge conformity), but not sufficient to prove bioequivalence. In this case bioassays or pharmacological studies, which measure therapeutically relevant activity, should be used. A phytogeneric is only comparable to the innovator preparation under the following conditions: (i) pharmaceutical equivalence (standardization), (ii) biopharmaceutical equivalence (in vitro dissolution), (iii) bioequivalence with different endpoints (in vitro model, animal model) or (iv) clinical study. An uncritical substitution of herbal drug preparations without considering these scientific criteria should be avoided.
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