The influence of antineoplaston A5 on particular subtypes of central dopaminergic receptors

A new therapeutic strategy for the treatment of Parkinson's disease (PD) is based on providing trophic support for degenerating dopaminergic (DA) neurons. It can be accomplished by administration of neurotrophic factors, or inducing astrocytes to differentiate and produce such factors. Antineoplaston A5 (A5), which is a naturally-occurring cytodifferentiating agent, may induce astrocytes to undergo normal differetiation, produce neurotrophic factors and alleviate the symptoms of PD. This paper describes studies on the influence of A5 on subtypes of central DA receptors by measuring the potency of haloperidol catalepsy in rats. A5, D1 agonist, and D1 D2 antagonists were given i.p. and D2 agonist s.c. for three consecutive days. Haloperidol catalepsy was measured by the method of Costall and Nylor. The degree of catalepsy was assessed every 30 min for 24 h and statistically evaluated using the Student's t-test. The results confirmed that A5 significantly attenuated catalepsy and stimulates dopamine D2 receptors. It reverses catalepsy induced by haloperidol and D2 antagonists, but increases cataleptogenic activity if given in combination with the D2 agonist. This leads to the conclusion that A5 as a naturally-occurring agent neutralizes both hyper- and hypoactivity of central dopaminergic structures. Besides possible use as an antiparkinsonism agent, A5 may find application in the treatment of other disturbances of dopaminergic transmission.