Rolitetracycline, launched in the late 1950s, was the first of the semi -synthetic tetracyclines. Rolitetracycline is formed by a Mannich condensation of formaldehyde and pyrrolidine with tetracycline. Rolitetracycline is a pro -drug of tetracycline, in which the pyrrolidine moiety improves bioavailability compared with tetracycline. Rolitetracycline has broad spectrum Gram positive activity in vivo, but pH instability limits use to parenteral administration. Rolitetracycline passively diffuses through porin channels in the bacterial membrane and reversibly binds to the 30S ribosomal subunit, preventing binding of tRNA to the mRNA-ribosome complex, and thus interfering with protein synthesis.